Actualización en fibrosis quística: uso de exacaftor/tezacaftor/ivacaftor/en pacientes con fibrosis quística port-trasplante pulmonar / Use of exacaftor/tezacaftor/ivacaftor in cystic patients post lung transplantation

El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.

The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.

Approach and anesthetic management for kidney transplantation in a patient with bilateral lung transplantation: case report

Abstract Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.

Características clínicas y resultados de pacientes con fibrosis quística con enfermedad pulmonar avanzada: experiencia en 10 años del Instituto Nacional del Tórax / Clinical features and outcomes of cystic fibrosis patients with advanced lung disease: experience of 10 years at the Instituto Nacional del Tórax

La enfermedad pulmonar avanzada (EPAV) es la principal causa de morbimortalidad en pacientes con Fibrosis Quística (FQ). Objetivo: describir características clínicas de pacientes con FQ con EPAV y mortalidad en el seguimiento. Método: Estudio descriptivo, retrospectivo de pacientes con FQ y EPAV: VEF1 4 años de vida. Un 75% era portador de infección crónica por Pseudomonas. Un 68% era dependiente de oxígeno y un 18% de ventilación mecánica no invasiva. El 70 % tuvo 2 o más hospitalizaciones el último año de seguimiento. De 27 pacientes derivados a trasplante, 7 se trasplantaron, 3 fallecieron en lista para trasplante, 9 presentaron alguna contraindicación: 4 de ellos por desnutrición y 5 por mala adherencia y escasa red de apoyo. En el seguimiento un 32% (n = 14) falleció, 93% de causa respiratoria. Conclusión: Un 39% de los pacientes tenían EPAV cuyo diagnóstico de FQ en promedio fue a los 11,2 años (SD ± 13 a). Las barreras de ingreso a lista para trasplante fueron: desnutrición, mala adherencia y falta de red de apoyo. Esta es una población con una elevada mortalidad.

Advanced cystic fibrosis lung disease (ACFLD) is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Objective: to describe clinical characteristics of patients with CF with ACFLD and mortality during follow-up. Method: Descriptive, retrospective study of patients with CF and ACFLD: FEVi < 40%, oxygen dependent, and/or referred to a lung transplantprogram. Clinical, microbiological, functional, genetic and mortality characteristics were collected. Results: Of 111 controlled patients, 39% met criteria for ACFLD. 52% were men and the mean age was 29,8 years- old. The average BMI was 19.9 kg/m2, 72% had pancreatic insufficiency and 87% had a genetic study, being the DF508 mutation the most frequent (67%). The average age of diagnosis was 11.2 years (SD ± 13 years), being in 54,5% over the age of 4 years. 75% had chronic Pseudomonas infection. 68% were oxygen dependent and 18% on noninvasive mechanical ventilation. In the last year of follow-up 70% had 2 or more hospitalizations. Of 27 patients who have been referred for transplantation, 7 underwent lung transplantation, 3 died waiting on the transplant list, 9 had contraindications: 4 due to malnutrition and 5 to poor adherence and poor support network. 32% (n = 14) of the ACFLD patients died, 93% due to respiratory causes. Conclusion: 39% of the patients had ACFLD. The average age for CF diagnosis was 11.2 years (SD ± 13 years) Barriers to entering the transplant list are: malnutrition, poor adherence, and lack of a support network. This is a population with a high mortality.

Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil

OBJECTIVES: To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. METHODS: We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. RESULTS: From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. CONCLUSION: The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

Trasplante pulmonar en pacientes con fibrosis quística / Lung transplantation in cystic fibrosis patients

Respiratory failure is the leading cause of morbidity and mortality in patients with cystic fibrosis. Lung transplantation (LT) is the choice for those with advanced respiratory failure. LT improves the quality of life and survival of these patients. Pretransplant colonization by resistant germs such as Pseudomona aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), are not a contraindication to transplantation. Patients infected with Burkholderia cepacia complex (Bcc) and especially those colonized with Burkhorderia cenocepacia have higher mortality after transplantation and are considered an absolute contraindication to transplantation in most centers in the world. The causes of death after transplant are surgical complications, primary graft dysfunction and infections in the first month, and chronic rejection and infection not associated with CMV after the first year. An early referral and multidisciplinary management in the pre andpost transplantation including rehabilitation, physiotherapy, and nutritional management are essential to achieve successful transplantation outcomes.

La falla respiratoria es la principal causa de morbimortalidad en pacientes con Fibrosis Quística. El trasplante pulmonar (TP) es la opción para aquellos con falla respiratoria avanzada. El TP mejora la calidad de vida y la sobrevida de estos pacientes. La colonización pretrasplante por gérmenes resistentes como Pseudomona Aureginosa y Staphylococcus aureus meticilino resistente (SAMR), no son contraindicación para trasplante. Pacientes infectados por el complejoBurkholderia cepacia (Bcc) especialmente aquellos colonizados con Burkholderia cenocepacia tienen mayor mortalidad post trasplante y es considerada una contraindicación absoluta para trasplante en la mayoría de los centros en el mundo. Las causas de muerte en el primer mes post trasplante son las complicaciones quirúrgicas, disfunción primaria de injerto e infecciones, después del primer año son rechazo crónico e infecciones no asociadas a CMV. Una derivación precoz y un manejo multidisciplinario en el pre y post trasplante que incluya rehabilitación, kinesioterapia, manejo nutricional son esenciales para el éxito del trasplante.

Tratamiento de la fibrosis quística, pasado y presente / Cystic fibrosis treatment, past and present

The treatment of cystic fibrosis is today mainly symptomatic. However, some positive results are been shown in pharmacotherapy, which seeks to correct the expression of the defect in CFTR. Given the low prevalence of the disease and the specific treatment required it is very important to have specialized centers that guarantee high quality care. These centers must include a multidisciplinary team involving the family and the patient. It remains vital nutritional support, early and aggressive antibiotic therapy and the removal of secretions from the airway.

El tratamiento de la fibrosis quística es hoy en día principalmente sintomático. Sin embargo, están apareciendo resultados positivos en la farmacoterapia, la cual busca corregir la expresión del defecto genético. Dado la baja prevalencia de la enfermedad y su tratamiento tan específico es muy importante contar con un centro especializado para su manejo a fin de otorgar una alta calidad de atención. Para este centro se requiere un equipo multidisciplinario que involucre a la familia y el paciente. Siguen siendo de vital importancia el soporte nutricional, el tratamiento antibiótico precoz y agresivo y la eliminación de las secreciones de la vía aérea.

Pediatric lung transplantation: 10 years of experience

Lung transplantation is a well-established treatment for advanced lung diseases. In children, the diseases that most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis. However, the number of pediatric lung transplantations being performed is low compared with the number of transplants performed in the adult age group. The objective of this study was to demonstrate our experience with pediatric lung transplants over a 10-year period in a program initially designed for adults.

Anaesthesia conflict for emergency laparoscopy appendectomy in cystic fibrosis

A thirty-one years old gentleman presented for emergency laparoscopic appendectomy. The patient had multiple hospital admissions due to frequent respiratory tract infections associated with cystic fibrosis [CF]. The patient had severe productive cough and widespread coarse crepitations and wheezes. A recent large burned area was noticed on the lumbosacral region. General anaesthesia [GA] was the only anesthetic option available for this patient to undergo the emergency laparoscopy appendectomy despite his bad chest condition. The patient was discharged home after 96 hours, following an uneventful postoperative period

Síndrome de obstrucción intestinal distal en pacientes adultos con fibrosis quística: Casos clínicos / Distal intestinal obstruction syndrome: Report of two cases with cystic fibrosis

Distal Intestinal Obstruction Syndrome (DIOS) has a 16 percent incidence among patients with Cystic Fibrosis (CF). It is characterized by an intestinal obstruction secondary to fecal impaction in distal ileum or cecum. We report two adult patients with DIOS. A female with CF and subjected to lung transplantation at the age of 13 years old. Five years later, she consulted for an intestinal obstruction. She was treated conservatively with a good clinical evolution. She had a new episode of DIOS eight months later that was also treated conservatively. A 31 year-old mole, subjected to bilateral lung transplantation nine years before, that was admitted to the hospital for a bronchiolitis. Three days after admission he started with an intestinal obstruction that was diagnosed as a DIOS. He was managed conservatively with a good clinical response.

Concomitant cryptococcosis and burkholderia infection in an asymptomatic lung transplant patient with cystic fibrosis

Concomitant pulmonary infections with Cryptococcus neoformans and Burkholderia cepacia in lung transplant recipients are very rare and create unique diagnostic and therapeutic dilemmas. Herein, we present a double lung transplant patient with cystic fibrosis who was found to have coinfection with these two rare organisms, though he was completely asymptomatic

Lung transplantation in india: a possible treatment option.

The burden of chronic respiratory diseases in India is on the rise, accounting for nearly 1 in 10 deaths. Chronic obstructive pulmonary disease is highly prevalent in India and is projected to be the third leading cause of deaths worldwide by 2020. Improved access to healthcare and better imaging modalities have led to an increase in the diagnosis of pulmonary fibrosis and cystic fibrosis in India. For these end-stage lung diseases, lung transplantation is an effective and established treatment option in North America and Europe. The indications, techniques, outcomes and complications of lung transplantation are well documented. The criteria for recipient/donor selection are now better defined and the surgical technique has improved over the past 2 decades. Based on our experience of setting up a lung transplantation programme, we have outlined the resources required for the perioperative and postoperative management of such patients.

Fibrosis quística: ¿cuándo referir un niño para trasplante pulmonar? / Lung transplant referral in child patients with cystic fibrosis

La fibrosis quística (FQ) es la enfermedad autosómica recesiva mas frecuente en niños en los Estados Unidos de América (EUA). Pese a los grandes avances de la medicina, la edad promedio de sobrevida en EUA es 32,9 años. La causa mas común de muerte es la enfermedad pulmonar, siendo el trasplante pulmonar la única solución para los estados mas avanzados. Las indicaciones para trasplante varían según cada centro; estas incluyen: fracaso a terapia médica, pobre calidad de vida, capacidad de los sistemas de salud de proveer medicamentos, terapias y cuidados. Por otra parte muchas de las contraindicaciones han ido cambiando y se analizan de manera individual. La transferencia debe ser temprana, con una adecuada comunicación para establecer metas apropiadas. El reciente puntaje para asignación de pulmones permite clasificar a los pacientes según edad, riesgos y probabilidad de fracaso. Debe reconocerse que el trasplante pulmonar pediátrico en FQ es una forma de prolongar la vida en algunos casos, pero significa cambiar una enfermedad por otra.

Lung transplantation

Transplantation of organs is the great adventure of this century. Alexis Carrel developed methods of joining blood vessels, which made the transplantation of organs feasible. Demikhov performed the first intra-thoracic canine lung and heart transplantation in the 1940s. In the early 1950s, Metras demonstrated that canine lung transplantation is technical feasible. In 1963, the first human lung transplant was performed and during the subsequent 15 years, about 40 clinical lung transplants were performed around the world. Successful lung transplant was achieved in 1982. The discovery of cyclosporine and its use as an immunosuppressant drug permitted prolonged survival in all transplanted organs especially in lung transplants. At present, lung transplantation is successfully used worldwide The remarkable progress and improved results in lung transplantation is due to superior immunosuppression strategies, improved donor and recipient selection, new antibiotics, improved strategies of preservation using prostaglandine E1 have decreased reperfusion injury, and prevention of post-operative sepsis due to bacterial, fungal, viral and parasitic infections, especially in cystic fibrosis. Heart-lung transplant is indicated for patients with pulmonary vascular disease, congenital heart disease and cystic fibrosis. These represent 72% of indications. Double lung transplant is reserved for bilateral lung anomalies without consequences on cardiac function: infectious diseases, bronchiectasies, cystic fibrosis, lymphangioleiomyomatosis, bronchioloalveolar carcininoma, and emphysema. Single lung transplant is reserved for patients who have no infection of their native lungs such as primary pulmonary hypertension without cardiac insufficiency, idiopathic fibrosis, histiocytosis X and emphysema without distension. The operative mortality rate is in the range of 10%. The five-year survival rate is about 60%. Despite advances in treatment of complications such as infection and chronic rejection, they are still responsible for half of the deaths after transplantation. However, in young patients with end-stage lung disease, lung transplantation is the sole treatment. [Heart Views. 2001;2[2]: 53-56] ' 2001 Hamad Medical Corporation