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.

Ex vivo lung perfusion in Brazil / A experiência brasileira na perfusão pulmonar ex vivo

Objective: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.

Objetivo: Avaliar o emprego da técnica de perfusão pulmonar ex vivo (PPEV) clinicamente com a finalidade de transplante. Métodos: Estudo prospectivo envolvendo o recondicionamento de pulmões limítrofes, definidos por critérios específicos, tais como relação PaO2/FiO2 < 300 mmHg, com um sistema de PPEV. Entre fevereiro de 2013 e fevereiro de 2014, os pulmões de cinco doadores foram submetidos à PPEV por até 4 h. Durante a PPEV, a mecânica pulmonar foi avaliada continuamente. Amostras do perfusato foram colhidas a cada hora, assim como foi realizada a avaliação funcional dos órgãos. Resultados: A média de PaO2 dos pulmões captados foi de 262,9 ± 119,7 mmHg, sendo que, ao final da terceira hora de perfusão, essa foi de 357,0 ±108,5 mmHg. A capacidade de oxigenação dos pulmões apresentou discreta melhora durante a PPEV nas primeiras 3 h (246,1 ± 35,1; 257,9 ± 48,9; e 288,8 ± 120,5 mmHg, respectivamente), sem diferenças significativas entre os momentos (p = 0,508). As médias de complacência estática foram de, respectivamente, 63.0 ± 18,7; 75,6 ± 25,4; e 70,4 ± 28,0 mmHg após 1, 2 e 3 h, com melhora significativa entre a hora 1 e 2 (p = 0,029), mas não entre a hora 2 e 3 (p = 0,059). A resistência vascular pulmonar permaneceu estável durante a PPEV, sem diferenças entre os momentos (p = 0,284). Conclusões: Os pulmões avaliados permaneceram em condições fisiológicas de preservação; no entanto, o protocolo não foi efetivo para promover a melhora na função pulmonar, inviabilizando o transplante.

Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system

OBJECTIVE: This study evaluated the performance of lungs that were preserved with different solutions (Celsior, Perfadex or saline) in an ex vivo rat lung perfusion system. METHODS: Sixty Wistar rats were anesthetized, anticoagulated and randomized into three groups (n = 20). The rats were subjected to antegrade perfusion via the pulmonary artery with Perfadex, Celsior, or saline, followed by 6 or 12 hours of ischemia (4ºC, n = 10 in each group). Respiratory mechanics, gas exchange and hemodynamics were measured at 10-minute intervals during the reperfusion of heart-lung blocks in an ex vivo system (IL2-Isolated Perfused Rat or Guinea Pig Lung System, Harvard Apparatus, Holliston, Massachusetts, USA; Hugo Sachs Elektronik, Germany) for 60 minutes. The lungs were prepared for histopathology and evaluated for edema following reperfusion. Group comparisons were performed using ANOVA and the Kruskal-Wallis test with a 5% level of significance. RESULTS: Gas exchange was not significantly different between lungs perfused with either Perfadex or Celsior at the same ischemic times, but it was very low in lungs that were preserved with saline. Airway resistance was greater in the lungs that were preserved for 12 hours. Celsior lungs that were preserved for 6 and 12 hours exhibited lower airway resistance (p = 0.01) compared to Perfadex lungs. Pulmonary artery pressure was not different between the groups, and no significant differences in histopathology and apoptosis were observed between the groups. CONCLUSIONS: Lungs that were preserved with Celsior or Perfadex exhibited similar gas exchange and histopathological findings. Airway resistance was slightly lower in the Celsior-preserved lungs compared with the Perfadex-preserved lungs.

The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE: Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance. METHODS: A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated. RESULTS: Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05). CONCLUSION: Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Estudo dos efeitos da prednisona sobre o sistema mucociliar de ratos / Effects of prednisone on mucociliary system of rats

INTRODUÇÃO: As infecções pulmonares constituem uma das principais causas de morbidade e mortalidade após o transplante pulmonar. O transplante expõe a árvore brônquica a uma série de condições, como à lesão de secção e anastomose brônquica e à ação dos imunossupressores, alterando os componentes do epitélio mucociliar. O sistema mucociliar presente nas vias aéreas do sistema respiratório é o principal mecanismo de defesa do trato respiratório, assim a influência de drogas neste sistema precisa ser investigada. A prednisona é um importante corticosteróide usado após o transplante de pulmão, no entanto seu uso pode estar associado ao aumento da mortalidade no período pós por complicações como baixa cicatrização e infecções. Desta forma, o objetivo deste estudo foi avaliar os efeitos da secção brônquica e da terapia com prednisona na depuração mucociliar. MÉTODOS: Foram utilizados 180 ratos machos Wistar distribuídos em 6 grupos (P1, P2, P3, ScP2, ScSal e Sal). Os animais dos grupos P1, P2 e P3 receberam diferentes doses de prednisona (0,625, 1,25 e 2,5 mg/kg/dia); os do grupo ScP2 foram submetidos à cirurgia de secção e anastomose brônquica e terapia com 1.25 mg/kg/dia de prednisona; do grupo ScSal foram submetidos à cirurgia de secção e anastomose brônquica e gavagem diária de solução fisiológica; por fim, os animais do grupo Sal receberam gavagem de solução fisiológica. Após o período de tratamento (7, 15 ou 30 dias), os animais foram sacrificados, e as medidas de frequência de batimento ciliar (FBC), velocidade de transporte mucociliar (VTMC) e transportabilidade do muco (TM) coletadas. Para avaliar os efeitos da droga realizamos a análise estatística comparativa entre os grupos P1, P2, P3 e Sal. Para avaliar a possível interação da droga com o procedimento cirúrgico comparamos os grupos ScP2, ScSal e P2. RESULTADOS: A administração das diferentes doses de prednisona...

INTRODUCTION: Infections have been and still are the major cause of morbidity and mortality after lung transplantation. Since mucociliary clearance (MCC) plays an important role on the human defense mechanism, the influence of drugs on MCC of patients submitted to lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy (P) on mucociliary clearance. METHODS: 180 rats were assigned to 6 groups (P1, P2, P3, ScSal, e Sal) according to surgical procedure or drug therapy: P1 (0.625mg/kg/day), P2 (1.25 mg/kg/day), P3 (2.5mg/kg/day), ScP2 (bronchial section and reanastomosis + 1.25 mg/kg/day ), Sal (saline solution 2ml/day) and ScSal (bronchial section + saline solution 2ml/day). After 7, 15 or 30 days they were killed and lungs were removed from thoracic cavity. Mucociliary transport velocity (MCTV), ciliary beting frequency (CBF) and mucus transportability (MT) were evaluated. RESULTS: The administration of different doses of prednisone studied harmed MT and the highest dosage (P3) decreased MCTV. FBC and MCTV was significantly impaired 7 and 15 days after bronchial transection and reanastomosis (p<0.001), but they showed a partial recovery on the 30th day after surgery procedure. Prednisone therapy improved MT after surgery procedure (p<0,02). CONCLUSION: High dosages of prednisone affect mucociliary clearance. The Prednisone therapy after section and reanastomosis surgery not affect mucociliary clearance since, despite improving MT, the CBF and MCTV are not influenced.