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.

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

Presentamos una revisión de los aspectos bioéticos de la limitación al acceso a trasplante pulmonar en pacientes mayores de 65 años. El trasplante pulmonar supone una opción terapéutica en pacientes con enfermedades respiratorias graves en fase avanzada, progresivas a pesar de tratamiento médico con el objetivo de prolongar la supervivencia esperada. Se trata de un tratamiento quirúrgico agresivo para el paciente, que deberá cumplimentar un tratamiento inmunosupresor de por vida. Dada la escasez de donantes, el acceso a este tratamiento está regulado por las sociedades de trasplante de órgano, que realizan las guías de selección de pacientes. Entre las contraindicaciones al trasplante ha existido un límite de edad fijado en 65 años, sostenido por los malos resultados de los pacientes de mayor edad y siguiendo una bioética utilitarista. No existe un criterio unificado de selección en la actualidad que permita identificar a los pacientes de mayor edad susceptibles de tener peor resultado tras el trasplante. Aplicando una bioética personalista proponemos emplear criterios de selección basados en escalas de fragilidad del paciente para identificar aquellos pacientes con mayor fragilidad y mayor posibilidad de fallecer tras el trasplante

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, pro-gressive 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 pa-tients more likely to die after the transplant procederé

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.

Valoración de la tolerancia y seguridad de 5 modelos de sedación durante la realización de la ecobroncoscopia / Tolerance and Safety of 5 Models of Sedation During Endobronchial Ultrasound

Introducción: La sedación durante la ecobroncoscopia es importante debido a la duración prolongada de esta exploración. Evaluamos distintos modelos de sedación y sus complicaciones. Método: Se realizó un estudio multicéntrico, prospectivo y observacional en el que recogieron distintas variables en 307 pacientes con distintos modelos de sedación: a) midazolam en bolo; b)propofol en perfusión; c) midazolam en bolo y propofol en perfusión; d) propofol en perfusión y remifentanilo en perfusión, y e) midazolam en bolo y fentanilo en bolo. Finalizada la prueba, los pacientes contestaron una encuesta de satisfacción. Resultados: Los pacientes por modelo de sedación fueron: A 24, B 37, C 107, D 62 y E 77. Las puntuaciones de las sensaciones percibidas de recuerdo, dolor, tos, disnea y exploración prolongada (0,65 ± 1,11; 0,3 ± 0,73; 0,46 ± 0,9; 0,29 ± 0,73; 0,59 ± 0,96) fueron menores frente a miedo y nerviosismo antes de la exploración (1,26 ± 1,37 y 1,5 ± 1,41). Los valores elevados de indiferencia ante la repetición (1,49 ± 1,3) y de sensación agradable de la prueba (1,23 ± 1,17), junto con cifras bajas la sensación de angustia (0,49 ± 0,85) e incomodidad de la exploración (0,62 ± 1,1), muestran que los distintos modelos de sedación fueron bien tolerados. El 46,6% de los pacientes no encontraron ningún momento malo y el 89,6% se repetiría la prueba. Los modelos E y C fueron los que menos complicaciones presentaron (12,9 y 31,7%) y, en todos los casos, se resolvieron con medidas terapéuticas sencillas. Conclusiones: Los modelos de sedación analizados fueron bien tolerados y la mayoría aceptarían la repetición de la ecobroncoscopia. Las complicaciones fueron escasas y sencillas de resolver

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 momento" 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

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.

Microangiopatía trombótica asociada a tacrolimus en trasplante pulmonar / Thrombotic Microangiopathy Associated With Tacrolimus in Lung Transplantation

La microangiopatía trombótica (MAT) es una complicación infrecuente asociada a los anticalcineurínicos en el trasplante pulmonar, independiente de la enfermedad de base de los pacientes trasplantados. Habitualmente se presenta como formas incompletas, lo que dificulta el diagnóstico, que suele ser tardío, provocando irreversibilidad de las lesiones. Es independiente del tiempo de trasplante y en muchos casos existe infección concomitante, lo que tiende a ocultar el diagnóstico. Los casos presentados comparten el agente causal y la presencia de infección concomitante. El tratamiento ha variado en los últimos años, recomendándose la plasmaféresis o, más recientemente, el anticuerpo eculizumab. No obstante, la retirada o cambio del anticalcineurínico causante es la medida más coste-efectiva. La MAT podría tratarse de una entidad infradiagnosticada a tener en cuenta en pacientes trasplantados

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

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.