Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. METHODS: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. RESULTS: Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p = .027) but failed on DNAemia/CMV infection (p = .148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p = .02). CONCLUSION: QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Flexible broncoscopy in patients in supportive therapy with oxygenation by extracorporeal membrane.

OBJECTIVE: To report the experience of performing bronchoscopy in patients who underwent supportive therapy with extracorporeal membrane oxygenation in whom the bronchoscopy was performed. METHODS: This was a review of medical records of patients diagnosed with extracorporeal membrane oxygenation and who required diagnostic or therapeutic bronchoscopy. Records included were related to patients admitted to the intensive care unit of Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo, between 2014 and 2020. RESULTS: During the study, 16 bronchoscopies were performed in 8 patients admitted to the intensive care unit and who underwent supportive therapy with extracorporeal membrane oxygenation. The mean age of patients was 28.37 years. Four patients were women (50%). A total of 5 (31.25%) therapeutic bronchoscopies and 11 (68.75%) diagnostics were performed. In 5 of patients, material was collected: 4 samples of bronchoalveolar lavage, three collections of transbronchial biopsies, and 1 of endobronchial biopsies. No patient had radiological worsening or hemodynamic complications. One patient (6.25%) had transient desaturation. There was moderate bleeding after transbronchial biopsy in 1 (6.25%) procedure, which was resolved endoscopically. CONCLUSION: Patients undergoing extracorporeal membrane oxygenation can safely perform diagnostic or therapeutic bronchoscopy provided that they have a detailed indication. Procedures were performed by a specialized bronchoscopy team in intensive care environment and with the assistance of a qualified multidisciplinary team in membrane oxygenation therapy extracorporeal.

Brazilian initial experience with lung transplantation due to irreversible lung fibrosis post-COVID-19 in a national reference center: a cohort study

ABSTRACT BACKGROUND: Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases. OBJECTIVES: To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil. DESIGN AND SETTING: Cohort study conducted at a national reference center for lung transplantation. METHODS: Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19. RESULTS: Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day. CONCLUSIONS: LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

Flexible broncoscopy in patients in supportive therapy with oxygenation by extracorporeal membrane

ABSTRACT Objective: To report the experience of performing bronchoscopy in patients who underwent supportive therapy with extracorporeal membrane oxygenation in whom the bronchoscopy was performed. Methods: This was a review of medical records of patients diagnosed with extracorporeal membrane oxygenation and who required diagnostic or therapeutic bronchoscopy. Records included were related to patients admitted to the intensive care unit of Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo, between 2014 and 2020. Results: During the study, 16 bronchoscopies were performed in 8 patients admitted to the intensive care unit and who underwent supportive therapy with extracorporeal membrane oxygenation. The mean age of patients was 28.37 years. Four patients were women (50%). A total of 5 (31.25%) therapeutic bronchoscopies and 11 (68.75%) diagnostics were performed. In 5 of patients, material was collected: 4 samples of bronchoalveolar lavage, three collections of transbronchial biopsies, and 1 of endobronchial biopsies. No patient had radiological worsening or hemodynamic complications. One patient (6.25%) had transient desaturation. There was moderate bleeding after transbronchial biopsy in 1 (6.25%) procedure, which was resolved endoscopically. Conclusion: Patients undergoing extracorporeal membrane oxygenation can safely perform diagnostic or therapeutic bronchoscopy provided that they have a detailed indication. Procedures were performed by a specialized bronchoscopy team in intensive care environment and with the assistance of a qualified multidisciplinary team in membrane oxygenation therapy extracorporeal.

Brazilian initial experience with lung transplantation due to irreversible lung fibrosis post-COVID-19 in a national reference center: a cohort study.

BACKGROUND: Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases. OBJECTIVES: To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil. DESIGN AND SETTING: Cohort study conducted at a national reference center for lung transplantation. METHODS: Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19. RESULTS: Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day. CONCLUSIONS: LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

A Brazilian university hospital position regarding transplantation criteria for HIV-positive patients according to the current literature.

Human immunodeficiency virus (HIV) infection was considered a contraindication for solid organ transplantation (SOT) in the past. However, HIV management has improved since highly active antiretroviral therapy (HAART) became available in 1996, and the long-term survival of patients living with HIV has led many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection.Based on the available data in the medical literature and the cumulative experience of transplantation in HIV-positive patients at our hospital, the aim of the present article is to outline the criteria for transplantation in HIV-positive patients as recommended by the Immunocompromised Host Committee of the Hospital das Clínicas of the University of São Paulo.

A Brazilian university hospital position regarding transplantation criteria for HIV-positive patients according to the current literature

Human immunodeficiency virus (HIV) infection was considered a contraindication for solid organ transplantation (SOT) in the past. However, HIV management has improved since highly active antiretroviral therapy (HAART) became available in 1996, and the long-term survival of patients living with HIV has led many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. Based on the available data in the medical literature and the cumulative experience of transplantation in HIV-positive patients at our hospital, the aim of the present article is to outline the criteria for transplantation in HIV-positive patients as recommended by the Immunocompromised Host Committee of the Hospital das Clínicas of the University of São Paulo.

The pulmonary microbiome: challenges of a new paradigm / Microbioma pulmonar: desafios de um novo paradigma

ABSTRACT The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.

RESUMO O estudo do microbioma humano - e, mais recentemente, o do sistema respiratório - através de sofisticadas técnicas de biologia molecular, desvendou a imensa diversidade de colonização microbiana nos seres humanos, sejam saudáveis, sejam portadores de diferentes doenças. Aparentemente, ao contrário do que se acreditava, existe uma colonização não patogênica dos pulmões por microrganismos, como bactérias, fungos e vírus. Esse microbioma pulmonar fisiológico apresenta uma densidade baixa de colônias, porém uma elevada diversidade; por outro lado, alguns estados patológicos levam a uma perda dessa diversidade, com aumento da concentração de alguns gêneros bacterianos em detrimento de outros. Ainda, além do conhecimento qualitativo das bactérias presentes no pulmão em diversos estados de saúde ou de doença, o conhecimento avança para o entendimento da interação que essa microbiota tem com o sistema imune local e sistêmico, modulando a resposta imunológica. Compreendendo essa intrínseca relação entre a microbiota e os pulmões, estudos apresentam novos conceitos sobre os mecanismos fisiopatogênicos da homeostase do sistema respiratório e a possível disbiose em estado de algumas doenças, como fibrose cística, DPOC, asma e doenças intersticiais. Essa quebra de paradigma do conhecimento da microbiota presente nos pulmões fez com que se torne premente entender melhor o papel do microbioma para identificar possíveis alvos terapêuticos e abordagens clínicas inovadoras. Através desse novo salto de conhecimento é que os resultados dos estudos preliminares poderão ser traduzidos em benefícios aos nossos pacientes.

The pulmonary microbiome: challenges of a new paradigm.

The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.

Assessment of Pulmonary Function before and after Sinus Surgery in Lung Transplant Recipients

Abstract Introduction The association between sinus and lung diseases is well known. However, there are scarce studies regarding the effects of sinus surgery on pulmonary function in lung transplant recipients. The present study describes our experience with sinus surgery in lung transplant recipients with chronic rhinosinusitis. Objectives To assess the impact of sinus surgery for chronic rhinosinusitis on pulmonary function and on inpatient hospitalization days due to lower respiratory tract infection in lung transplant recipients. Methods A retrospective study conducted between 2006 and 2012 on a sample of lung transplant recipients undergoing sinus surgery for chronic rhinosinusitis. Pulmonary function, measured by forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as well as inpatient hospitalization days due to lower respiratory tract infection, were compared 6 months before and 6 months after sinus surgery. Results The FEV1 values increased significantly, and the inpatient hospitalization days due to bronchopneumonia decreased significantly 6 months after sinus surgery. The preoperative and postoperative median FEV1 values were 2.35 and 2.68 respectively (p = 0.0056). The median number of inpatient hospitalization days due to bronchopneumonia 6 months before and 6 months after surgery were 32.82 and 5.41 respectively (p = 0.0013). Conclusion In this sample of lung transplant recipients with chronic rhinosinusitis, sinus surgery led to an improvement in pulmonary function and a decrease in inpatient hospitalization days due to bronchopneumonia.

Assessment of Pulmonary Function before and after Sinus Surgery in Lung Transplant Recipients.

Introduction The association between sinus and lung diseases is well known. However, there are scarce studies regarding the effects of sinus surgery on pulmonary function in lung transplant recipients. The present study describes our experience with sinus surgery in lung transplant recipients with chronic rhinosinusitis. Objectives To assess the impact of sinus surgery for chronic rhinosinusitis on pulmonary function and on inpatient hospitalization days due to lower respiratory tract infection in lung transplant recipients. Methods A retrospective study conducted between 2006 and 2012 on a sample of lung transplant recipients undergoing sinus surgery for chronic rhinosinusitis. Pulmonary function, measured by forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as well as inpatient hospitalization days due to lower respiratory tract infection, were compared 6 months before and 6 months after sinus surgery. Results The FEV1 values increased significantly, and the inpatient hospitalization days due to bronchopneumonia decreased significantly 6 months after sinus surgery. The preoperative and postoperative median FEV1 values were 2.35 and 2.68 respectively ( p = 0.0056 ). The median number of inpatient hospitalization days due to bronchopneumonia 6 months before and 6 months after surgery were 32.82 and 5.41 respectively ( p = 0.0013 ). Conclusion In this sample of lung transplant recipients with chronic rhinosinusitis, sinus surgery led to an improvement in pulmonary function and a decrease in inpatient hospitalization days due to bronchopneumonia.

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.

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.

Experience of Lung Transplantation in Patients with Lymphangioleiomyomatosis at a Brazilian Reference Centre.

INTRODUCTION: Lung transplantation (LT) is the standard of care for patients with advanced lung diseases, including lymphangioleiomyomatosis (LAM). LAM accounts for only 1% of all LTs performed in the international registry. As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited. METHODS: We conducted a retrospective review of all LAM patients who underwent LT at our centre between 2003 and 2016. Pre- and post-transplant data were assessed. RESULTS: Eleven women with LAM underwent LT, representing 3.3% of all procedures. Ten (91%) patients underwent double-LT. The mean age at diagnosis was 39 ± 6 years and the mean FEV1 before LT was 28 ± 14%. Only one patient underwent pleurodesis for recurrent pneumothorax. Pulmonary hypertension was confirmed in 3 (27%) patients. Four (36%) patients received sirolimus preoperatively; three of them received it until the day of LT, and there was no occurrence of bronchial anastomotic dehiscence after the procedure. Four patients (36%) received mTOR inhibitors post-transplant. The median follow-up from LT was 44 months. There were 3 deaths (27%) during the study and survival probabilities at 1, 3, and 5 years after LT were, 90, 90, and 77%, respectively. CONCLUSIONS: This data reinforces the role of LT for LAM patients with end-stage disease. The use of sirolimus seems to be safe before LT and the occurrence of complications after LT, including those LAM-related, should be continuously monitored.

Lung transplantation: overall approach regarding its major aspects / Transplante pulmonar: abordagem geral sobre seus principais aspectos

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.

RESUMO O transplante pulmonar é uma terapia bem estabelecida para pacientes com doença pulmonar avançada.A avaliação do candidato para o transplante é uma tarefa complexa e envolve uma equipe multidisciplinar que acompanha o paciente para além do período pós-operatório.O tempo médio atual em lista de espera para transplante pulmonar é de aproximadamente 18 meses no estado de São Paulo. Em 2014, dados da Associação Brasileira de Transplante de Órgãos mostram que 67 transplantes pulmonares foram realizados no Brasil e que 204 pacientes estavam na lista de espera para transplante pulmonar.O transplante pulmonar é principalmente indicado no tratamento de DPOC, fibrose cística, doença intersticial pulmonar, bronquiectasia não fibrocística e hipertensão pulmonar.Esta revisão abrangente teve como objetivos abordar os aspectos principais relacionados ao transplante pulmonar: indicações, contraindicações, avaliação do candidato ao transplante, avaliação do candidato doador, gestão do paciente transplantado e complicações maiores. Para atingirmos tais objetivos, utilizamos como base as diretrizes da Sociedade Internacional de Transplante de Coração e Pulmão e nos protocolos de nosso Grupo de Transplante Pulmonar localizado na cidade de São Paulo.