Rafael Medeiros Carraro

Bacterial and fungal pneumonias after lung transplantation.

OBJECTIVE The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms. MATERIALS AND METHODS We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007. RESULTS There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant. CONCLUSIONS Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.

Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports.

Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiologic entity characterized by typical neurologic symptoms with characteristic cerebral image alterations. It has been reported in solid organ transplantations, especially related to the use of calcineurin inhibitors. The incidence of PRES in lung transplantation is unknown and probably under-reported in the literature. Here we describe 5 cases of PRES after bilateral lung transplantation. One of the reported cases was the first in the literature in which the neurologic onset precluded the introduction of calcineurin inhibitor. Therefore, although calcineurin inhibitors are known to play an important role in the development of PRES in the setting of lung transplantation, other causes seems to be involved in the physiopathology of this syndrome.

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.

Fungal infection by Mucorales order in lung transplantation: 4 case reports.

Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donors segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients.

Transplante pulmonar: abordagem geral sobre seus principais aspectos.

O transplante pulmonar e uma terapia bem estabelecida para pacientes com doenca pulmonar avancada.A avaliacao do candidato para o transplante e uma tarefa complexa e envolve uma equipe multidisciplinar que acompanha o paciente para alem do periodo pos-operatorio.O tempo medio atual em lista de espera para transplante pulmonar e de aproximadamente 18 meses no estado de Sao Paulo. Em 2014, dados da Associacao Brasileira de Transplante de Orgaos mostram que 67 transplantes pulmonares foram realizados no Brasil e que 204 pacientes estavam na lista de espera para transplante pulmonar.O transplante pulmonar e principalmente indicado no tratamento de DPOC, fibrose cistica, doenca intersticial pulmonar, bronquiectasia nao fibrocistica e hipertensao pulmonar.Esta revisao abrangente teve como objetivos abordar os aspectos principais relacionados ao transplante pulmonar: indicacoes, contraindicacoes, avaliacao do candidato ao transplante, avaliacao do candidato doador, gestao do paciente transplantado e complicacoes maiores. Para atingirmos tais objetivos, utilizamos como base as diretrizes da Sociedade Internacional de Transplante de Coracao e Pulmao e nos protocolos de nosso Grupo de Transplante Pulmonar localizado na cidade de Sao Paulo.

Lung transplantation: overall approach regarding its major aspects.

ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil.

Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil.

INTRODUCTION Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Nonadherence to treatment in lung transplant recipients: a matter of life and death

Lung transplantation is a complex intervention, requiring strict adherence to a very specific medical regimen, which involves not only drug taking but also a fairly restrictive daily routine. The extent to which patients adhere to the prescribed regimen plays a key role in achieving optimal transplantation outcomes.

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.

Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience

BACKGROUND Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA) are known to increase the risk for chronic lung allograft dysfunction (CLAD). However, specific lung injury mechanisms are not clearly known. The objective of the study was to describe histopathological findings in surveillance lung transbronchial biopsies that can be correlated with episodes of BA in the lung allograft. METHODS This retrospective analysis of surveillance transbronchial biopsies was performed in lung transplant recipients, with available data of broncho-alveolar fluid (cultures and cytology), lung function parameters, and esophageal functional tests. RESULTS Were analyzed 11 patients, divided into 3 groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign material in lung biopsies. A histopathological pattern of neutrophilic bronchitis (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA group in 2 or more biopsy samples; culture samples were all negative; the 5 NB-positive patients developed CLAD and died (3/5) or needed re-transplantation (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both patients in the control group had transient NB in biopsies with positive cultures but remained free of CLAD. CONCLUSIONS Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux.