Utilization of Quantitative Computed Tomography Assessment to Identify Bronchiolitis Obliterans Syndrome After Single Lung Transplantation.

OBJECTIVE: To evaluate quantitative chest computed tomography (CT) methods for the detection of air trapping (AT) and to assess its diagnostic performance for the diagnosis of bronchiolitis obliterans syndrome (BOS) in single lung transplant (SLT) patients. METHODS: Adult patients who had a SLT at a single transplant center and underwent CT scan after transplantation were retrospectively included. CT findings of air trapping were measured by three different methods: expiratory air-trapping index (ATIexp), mean lung density on expiratory acquisition (MLDexp) and expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD). Sensitivity, specificity and diagnostic accuracy of the three methods for the detection of BOS status evaluated by serial routine measures of pulmonary function tests (gold standard) were assessed. RESULTS: Forty-six SLT patients (52.2% females, mean age 58 ± 6 years) were included in the analysis, 12 (26%) patients with a diagnosis of BOS. Quantitative CT diagnosis of AT ranged from 26 to 35%. Sensitivity, specificity and accuracy of each method for the detection of BOS were 85.7%, 84.7% and 85.0% for ATIexp, 78.5%, 93.4% and 90.0% for MLD and 64.2%, 89.1% and 83.3% E/I-ratio(MLD), respectively. CONCLUSION: Quantitative measures of AT obtained from standard CT are feasible and show high specificity and accuracy for the detection of BOS in SLT patients.

What is expected in lung function after lung transplantation due to end-stage pulmonary silicosis?

In this study, we aimed to determine the impact of lung transplantation (LTx) on pulmonary function tests (PFTs) and survival among patients with end-stage silicosis. We included patients with end-stage silicosis on the wait list for LTx, between January 1989 and July 2015 (N = 26). Sixteen of these patients received LTx; 10 were eligible, but did not undergo LTx (non-LTx) during the study period. Retrospective information on PFTs (spirometry [volumes and flows], 6-minute walking test [6MWT], and DLCO) was retrieved from patients' medical charts, including baseline information for all patients and follow-up information for the LTx. At baseline, most patients presented with spirometric and 6MWT values that were suggestive of severe disease (FEV1 /FVC 76.5 ± 29.7; 6MWT 267.4 ± 104.5 m). Significant increases in these values were observed at follow-up in the LTx (P = .036 and .151, respectively). The overall median survival of patients in the LTx and non-LTx was 3.35 years (95% CI: 0.16-14.38) and 0.78 years (95% confidence interval [CI]: 0.12-3.65) (P = 0.002), respectively. For patients with end-stage silicosis, LTx offers significant benefits regarding pulmonary function and survival when compared to non-LTx, and is a reliable tool to help this critical population of patients, whose only treatment option is LTx.

First reported case of cellulitis due to Cryptococcus gattii in lung transplantation recipient: a case report.

Cryptococcus gattii are closely related species of encapsulated yeast-like fungi involved in the etiology of cryptococcosis, especially in immunocompetent individuals. Dissemination with involvement of many organ systems is common. On the other hand, cellulitis in an immunossupressed patient caused by C. gattii is rare. We present a case of disseminated disease caused by Cryptococcus gattii in a lung transplant recipient who manifested cellulitis. The disease was also complicated by a lung carcinoma. We emphasize that cryptococcal cellulitis related to C. gattii in solid organ transplant (SOT) recipients should be considered in the differential diagnosis of acute bacterial skin infections.

Pulmonary rehabilitation improves survival in patients with idiopathic pulmonary fibrosis undergoing lung transplantation.

This study was conducted to evaluate whether a pulmonary rehabilitation program (PRP) is independently associated with survival in patients with idiopathic pulmonary fibrosis (IPF) undergoing lung transplant (LTx). This quasi-experimental study included 89 patients who underwent LTx due to IPF. Thirty-two completed all 36 sessions in a PRP while on the waiting list for LTx (PRP group), and 53 completed fewer than 36 sessions (controls). Survival after LTx was the main outcome; invasive mechanical ventilation (IMV), length of stay (LOS) in intensive care unit (ICU) and in hospital were secondary outcomes. Kaplan-Meier curves and Cox regression models were used in survival analyses. Cox regression models showed that the PRP group had a reduced 54.0% (hazard ratio = 0.464, 95% confidence interval 0.222-0.970, p = 0.041) risk of death. A lower number of patients in the PRP group required IMV for more than 24 hours after LTx (9.0% vs. 41.6% p = 0.001). This group also spent a mean of 5 days less in the ICU (p = 0.004) and 5 days less in hospital (p = 0.046). In conclusion, PRP PRP completion halved the risk of cumulative mortality in patients with IPF undergoing unilateral LTx.

Pulmonary Rehabilitation in Patients With Advanced Idiopathic Pulmonary Fibrosis Referred for Lung Transplantation.

PURPOSE: Currently, pulmonary rehabilitation (PR) has a weak recommendation for idiopathic pulmonary fibrosis (IPF) and is often recommended for mild to moderate disease. We aimed to investigate the completion rate of PR in patients with advanced IPF, to analyze whether the severity of disease influences PR response and whether there is any difference between subjects who are able or not able to successfully complete the program. METHODS: Patients with IPF referred to lung transplantation (n = 48) were enrolled in an outpatient PR program including 3 times/wk supervised exercise training during 12 wk. A short-form 36-item health-related quality-of-life (HRQL) questionnaire and 6-min walk test distance (6MWD) were evaluated before and after PR. RESULTS: We found that 64.5% of patients successfully completed PR (31/48). Baseline forced vital capacity (FVC) and lung diffusion capacity for carbon monoxide (DLCO) were 49% ± 13% and 46% ± 17% of predicted, respectively. There was no difference comparing those who did and did not complete PR. In the former group, 6MWD (58 ± 63 m) and several domains of the HRQL questionnaire improved significantly. No significant association was found between markers of disease severity (FVC, DLCO, and dyspnea) and improvement in clinical outcomes. CONCLUSIONS: Two-thirds of our sample with advanced IPF referred to lung transplant successfully attended PR and improved exercise capacity and HRQL, without association with markers of disease severity. No difference was found at baseline compared with subjects who were not able to complete the program.

The incidence of cytomegalovirus infection in lung transplant recipients under universal prophylaxis with intravenous ganciclovir.

The best strategy for control of cytomegalovirus (CMV) infection in lung transplant patients is still not determined. The aim of this study was to document the incidence of CMV infection in a cohort of lung transplant recipients under universal prophylaxis with intravenous ganciclovir. All patients received immunosuppressive regimens consisting of cyclosporine, azathioprine, and prednisone. Regardless of CMV serostatus, intravenous ganciclovir was prescribed for every patient in the first 3 months post-transplantation. CMV infection was defined as the detection of CMV pp65 in leukocytes. Eighty-two lung transplant patients were included over a 5-year period. The incidence of CMV infection in the first year post-transplantation was 68.3%, occurring after a median length of 114 days (range, 26-343 days). This study revealed a high incidence of CMV infection in the first year following lung transplantation despite prolonged universal ganciclovir prophylaxis.

Nocardia nova causing empyema necessitatis afterlung re-transplantation: a case report.

We report herein a case of thoracic infection due to Nocardia nova following lung re-transplantation performed for emphysema related to alpha-1-antitrypsin deficiency. The infection extended from the lung into the pleural space, thoracic wall, and mediastinum, presenting as pericarditis and empyema necessitatis. Nocardia nova was identified by 16S ribosomal deoxyribonucleic acid (rDNA) sequencing and phylogenetic analysis. According to a literature search of PubMed, LILACS and MEDLINE databases, we describe herein the first case of empyema necessitatis caused by N. nova species in a transplanted patient.

Comparison of the effect of two HMG CoA reductase inhibitors on LDL susceptibility to oxidation.

OBJECTIVE: To study the differences between fluvastatin and pravastatin regarding LDL susceptibility to oxidation, plasma levels of total cholesterol (TC), HDL-C, LDL-C and triglycerides (TG) in hypercholesterolemic patients with established coronary heart disease (CHD). METHODS: A double-blind randomized parallel study was conducted that included 41 hypercholesterolemic outpatients with CHD treated at the Instituto de Cardiologia do Rio Grande do Sul. The inclusion criteria were LDL-C above 100 mg/dL and triglycerides below 400 mg/dL based on 2 measures. After 4 weeks on a low cholesterol diet, those patients that fullfilled the inclusion criteria were randomized into 2 groups: the fluvastatin group (fluvastatin 40 mg/day) and the pravastatin group (pravastatin 20 mg/day), for 24 weeks of treatment. LDL susceptibility to oxidation was analyzed with copper-induced production of conjugated dienes (Cu2+) and water-soluble free radical initiator azo-bis (2'-2'amidinopropanil) HCl (AAPH). Spectroscopy nuclear magnetic resonance was used for determination of lipids. RESULTS: After 24 weeks of drug therapy, fluvastatin and pravastatin significantly reduced LDL susceptibility to oxidation as demonstrated by the reduced rate of oxidation (azo and Cu) and by prolonged azo-induced lag time (azo lag). The TC, LDL-C, and TG reduced significantly and HDL-C increased significantly. No differences between the drugs were observed. CONCLUSION: In hypercholesterolemic patients with CHD, both fluvastatin and pravastatin reduced LDL susceptibility to oxidation.

High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients.

OBJECTIVE: The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection. MATERIALS AND METHODS: We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2-5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22-59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision. RESULTS: The main HRCT pattern, found in 65% (n=15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n=3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n=5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n=3) of patients, and were associated with consolidation and ground-glass opacities in one case. CONCLUSION: The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients.

Twelve-year survival of the first living-donor pediatric lung transplantation in Brazil.

OBJECTIVE: To report the long-term follow-up of the first living-donor lobar lung transplantation performed in Latin America. DESCRIPTION: The patient was a 12-year-old boy with post-infectious obliterative bronchiolitis with end-stage pulmonary disease. He was on continuous oxygen support, presenting with dyspnea even during minimal activity. He underwent bilateral lobar lung transplantation with living donors. The procedure was performed with the left and right lower lobes of two different related donors. In the second side cardiopulmonary bypass was required. The transplant was uneventful, and the patient was extubated after 14 hours and discharged with 44 days, after resolution of infectious, immunological and drug-related complications. After 12 years of follow-up, he presents with adequate lung function and has resumed his habitual activities. COMMENTS: Living-donor lobar lung transplantation is a complex procedure feasible for the treatment of selected pediatric end-stage pulmonary disease. This particular population might benefit from this approach since the availability of pediatric donors is very scarce and the clinical course of pediatric advanced pulmonary disease may be unpredictable.

Prognostic factors in lung transplantation: the Santa Casa de Porto Alegre experience.

BACKGROUND: Lung transplantation (LT) has been established as a current therapy for selected patients with end-stage lung disease. Different prognostic factors have been reported by transplant centers. The objective of this study is to report our recent results with LT and to search for prognostic factors. METHODS: We performed a retrospective analysis of 130 patients who underwent LT at our institution from January 2004 to July 2009. Donor, recipient, intraoperative, and postoperative variables were collected. RESULTS: The mean age was 53.14 years (ranging from 8 to 72 years) and 80 (61.5%) were male. The main causes of end-stage respiratory disease were pulmonary fibrosis 53 (40.7%) and chronic obstructive pulmonary disease 52 (40%). The actuarial 1-year survival was 67.7%. Variables correlated with survival were age (P=0.004), distance in the 6-min walk test (P=0.007), coronary heart disease (P=0.001), cardiopulmonary bypass (P=0.02), intraoperative transfusion of red blood cells (P=0.016), increasing central venous pressure at 24th postoperative hour (P=0.001), increasing pulmonary capillary wedge pressure at 24th postoperative hour (P=0.01); length of intubation (P<0.01), reintubation (P=0.001), length of intensive care unit stay (P<0.001), abdominal complication (P=0.003), acute renal failure requiring dialysis (P<0.001), native lung hyperinflation (P=0.02), and acute rejection in the first month (P=0.03). In multivariate analysis, only dialysis (P=0.004, hazards ratio [HR] 2.68), length of intubation (P=0.004, HR 1.002 for each hour), and reintubation (P=0.003, HR 2.88) proved to be independent predictors. CONCLUSION: Analysis of variables in our cohort highlighted dialysis, longer mechanical ventilation requirement, and reintubation as independent prognostic factors in LT.

Nocardia nova causing empyema necessitatis afterlung re-transplantation: a case report

Abstract: We report herein a case of thoracic infection due to Nocardia nova following lung re-transplantation performed for emphysema related to alpha-1-antitrypsin deficiency. The infection extended from the lung into the pleural space, thoracic wall, and mediastinum, presenting as pericarditis and empyema necessitatis. Nocardia nova was identified by 16S ribosomal deoxyribonucleic acid (rDNA) sequencing and phylogenetic analysis. According to a literature search of PubMed, LILACS and MEDLINE databases, we describe herein the first case of empyema necessitatis caused by N. nova species in a transplanted patient.

Diagnosis of invasive aspergillosis in lung transplant recipients by detection of galactomannan in the bronchoalveolar lavage fluid.

BACKGROUND: Galactomannan (GM) detection in serum samples has been used to diagnose invasive aspergillosis (IA). Limited sensitivity has been observed in lung transplant recipients, for whom bronchoalveolar lavage (BAL) testing has been advocated. Because airway colonization with Aspergillus species occurs frequently in these patients, false-positive GM results have been reported if the cutoff validated for sera is used (i.e., 0.5). METHODS: Herein, we prospectively studied BAL fluid samples from 60 lung transplant patients to determine the optimal cutoff for BAL GM testing. Only one sample per patient was studied. BAL samples were vortexed and processed according to the manufacturer's instructions for serum samples. Sensitivity, specificity, and likelihood ratios were calculated in reference to proven or probable IA cases using receiver operating characteristic analysis. RESULTS: Eight patients had IA during the study (incidence 13.3%), including four patients with proven IA. Aspergillosis increased 5-fold the risk of death in lung transplant recipients. The positive predictive value of a positive BAL GM test at the 0.5 cutoff was low (24.2%). Raising the cutoff improved test specificity without compromising sensitivity. The best cutoff was defined at 1.5 (sensitivity 100% and specificity 90.4%). CONCLUSIONS: This study reinforces the importance of BAL GM testing in lung transplant recipients, particularly to exclude the diagnosis of IA. To minimize the frequency of false-positive results, a higher test cutoff should be applied to BAL samples, in comparison with serum samples.

Synchronous pulmonary and hepatic nodules in a patient with previous bronchogenic carcinoma: the relevance of histopathological confirmation.

The synchronous presentation of pulmonary and hepatic nodules in a patient with previously resected bronchogenic carcinoma raises suspicion of recurrence and mandates restaging. We present the case of a 71-year-old male with a history of lobectomy with pericardial resection and mediastinal lymphadenectomy (T3N0M0). At five years after the operation, he presented with a new pulmonary lesion. Restaging detected a synchronous nodule in the liver. Despite the strong suspicion of tumor recurrence, further investigation with a percutaneous liver biopsy revealed hepatocellular carcinoma. In order to investigate the etiology of the pulmonary lesion (hypotheses of recurrent bronchial cancer and of metastatic hepatocellular carcinoma), an open lung biopsy was performed, which revealed chronic inflammatory tissue with foci of anthracosis and dystrophic calcification. The patient was submitted to a non-anatomic resection of the liver lesion. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. This report highlights the relevance of the histopathological diagnosis in patients with a history of bronchogenic carcinoma and suspicion of tumor recurrence. Differential diagnoses and the treatment administered are discussed.

Surgical maneuvers for the management of bronchial complications in lung transplantation.

BACKGROUND: Many advances have substantially improved the clinical results of lung transplantation. However, the incidence of bronchial complications is still high, with significant impact on survival and limited interventional strategies for complex cases. Our aim is to evaluate the surgical management of bronchial complications following lung transplantation. METHODS: From May 1989 to June 2007, 251 patients were submitted to lung transplantation at our institution. In five cases, the bronchial complications observed were dealt with open surgical procedures. RESULTS: Complications surgically dealt were one broncho-arterial fistula and four stenosis. One left upper sleeve lobectomy, one right upper sleeve lobectomy and three segmental bronchial resections with anastomosis were performed. In all five cases the surgical procedure was successful and optimal bronchial healing was observed. Three patients died due to causes unrelated to the bronchial anastomosis 5, 21 and 32 months after the bronchoplastic procedure. Two patients are still alive and functionally well at 52 and 70 months post-bronchoplasty. CONCLUSIONS: Surgical management of bronchial complications after lung transplantation may be the last resort in complex, recalcitrant cases, nevertheless it is a feasible procedure and can provide good results not only on short- but also long-term follow-up.

Complications related to lobectomy in living lobar lung transplant donors.

OBJECTIVE: To evaluate post-operative complications in living lobar lung transplant donors. METHODS: Between September of 1999 and May of 2005, lobectomies were performed in 32 healthy lung transplant donors for 16 recipients. The medical charts of these donors were retrospectively analyzed in order to determine the incidence of postoperative complications and alterations in pulmonary function after lobectomy. RESULTS: Twenty-two donors (68.75%) presented no complications. Among the 10 donors presenting complications, the most frequently observed complication was pleural effusion, which occurred in 5 donors (15.6% of the sample). Red blood cell transfusion was necessary in 3 donors (9.3%), and 2 donors underwent a second surgical procedure due to hemothorax. One donor presented pneumothorax after chest tube removal, and one developed respiratory infection. There were two intra-operative complications (6.25%): one donor required bronchoplasty of the middle lobe; and another required lingular resection. No intra-operative mortality was observed. Post-operative pulmonary function tests demonstrated an average reduction of 20% in forced expiratory volume in one second (p < 000.1) compared to pre-operative values. CONCLUSIONS: Lobectomy in living lung transplant donors presents high risk of post-operative complications and irreversible impairment of pulmonary function. Careful pre-operative evaluation is necessary in order to reduce the incidence of complications in living lobar lung transplant donors.

Sobrevida de 12 anos do primeiro transplante pulmonar pediátrico intervivos do Brasil / Twelve-year survival of the first living-donor pediatric lung transplantation in Brazil

OBJETIVO: Apresentar o acompanhamento a longo prazo do primeiro caso de transplante pulmonar intervivos realizado na América Latina. DESCRIÇÃO: Paciente do sexo masculino, com 12 anos de idade, portador de bronquiolite obliterante com doença pulmonar avançada. Fazia uso de oxigênio domiciliar contínuo, com dispneia aos mínimos esforços. Foi submetido a transplante pulmonar bilateral com doadores vivos. A cirurgia foi realizada utilizando os lobos inferiores esquerdo e direito de dois doadores diferentes e com grau de parentesco com o receptor. No segundo lado (direito), foi necessário emprego de circulação extracorpórea. O transplante não teve intercorrências, e o paciente foi extubado com 14 horas de pós-operatório; com 44 dias, recebeu alta hospitalar, após a resolução de complicações infecciosas, imunológicas e medicamentosas. Após 12 anos de seguimento, encontra-se com função pulmonar preservada e desempenha normalmente suas atividades. COMENTÁRIOS: O transplante pulmonar intervivos é um procedimento de alta complexidade que pode contribuir para o tratamento de algumas pneumopatias na infância. Essa população se beneficia dessa abordagem, uma vez que a disponibilidade de doadores pediátricos é muito rara, e as pneumopatias pediátricas tendem a seguir um curso imprevisível.

OBJECTIVE: To report the long-term follow-up of the first living-donor lobar lung transplantation performed in Latin America. DESCRIPTION: The patient was a 12-year-old boy with post-infectious obliterative bronchiolitis with end-stage pulmonary disease. He was on continuous oxygen support, presenting with dyspnea even during minimal activity. He underwent bilateral lobar lung transplantation with living donors. The procedure was performed with the left and right lower lobes of two different related donors. In the second side cardiopulmonary bypass was required. The transplant was uneventful, and the patient was extubated after 14 hours and discharged with 44 days, after resolution of infectious, immunological and drug-related complications. After 12 years of follow-up, he presents with adequate lung function and has resumed his habitual activities. COMMENTS: Living-donor lobar lung transplantation is a complex procedure feasible for the treatment of selected pediatric end-stage pulmonary disease. This particular population might benefit from this approach since the availability of pediatric donors is very scarce and the clinical course of pediatric advanced pulmonary disease may be unpredictable.