RESUMO
: Probe-based confocal laser endomicroscopy (pCLE) was performed in 15 patients with emphysema and 15 healthy subjects to visualise small airways in a direct and dynamic way. Morphometry shows that the median cross-sectional area of the alveolar openings at the level of the alveolar ducts is significantly larger in emphysema (7.2×104 µm2) as compared with healthy subjects (5.2×104 µm2) (p=0.0002). Normalised autofluorescence intensity histograms show a decrease in median autofluorescence intensity (mAFI) in emphysema (p=0.001). mAFI correlates well with Tiffeneau index (r=0.66, p=0.007, 95% CI 0.21 to 0.88). Autofluorescence intensity in emphysema correlates with corresponding data of CT-based quantification. pCLE-based morphometry and autofluorescence intensity analysis in emphysema is able to detect regional changes inside the 'quiet zone'. TRIAL REGISTRATION NUMBER: Results, NCT01204970.
Assuntos
Broncoscopia/métodos , Microscopia Confocal/métodos , Enfisema Pulmonar/diagnóstico por imagem , HumanosRESUMO
Graft failure represents a leading cause of mortality after organ transplantation. Acute late-onset graft failure has not been widely reported. The authors describe the demographics, CT imaging-pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large-volume centers. Acute late-onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13-36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground-glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late-onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.
Assuntos
Bronquiolite Obliterante/etiologia , Rejeição de Enxerto/etiologia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/etiologia , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/patologia , Líquido da Lavagem Broncoalveolar/química , Oxigenação por Membrana Extracorpórea , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Transplante HomólogoRESUMO
Administration of azole antifungals to tacrolimus-treated solid organ recipients results in a major drug-drug interaction characterized by increased exposure to tacrolimus. The magnitude of this interaction is highly variable but cannot currently be predicted. We performed a retrospective analysis of 126 solid organ recipients (95 lung, 31 kidney) co-treated with tacrolimus and voriconazole (n = 100) or posaconazole (n = 26). Predictors of the change in tacrolimus dose-corrected trough concentrations (C/D) between baseline and tacrolimus-azole co-therapy were assessed using linear mixed modeling. Patients were genotyped for relevant polymorphisms in CYP3A4, CYP3A5, MDR1, CYP2C19, POR, and UGT1A4. Tacrolimus C/D increased by a factor 5.0 ± 2.7 (range 1.0-20.2) for voriconazole and 4.4 ± 2.6 (range 0.9-18.0) for posaconazole, suggesting that a 66% dose reduction is insufficient for the majority of patients. Change in C/D was blunted in CYP3A5 expressors (estimated effect: -43%, p = 0.017) and affected by hematocrit (+8% per %, p = 0.004), baseline C/D (-14% per 100% increase, p < 0.001), and age (+1%, p = 0.008). However, the final model explained only 22% of interindividual variability in C/D change. In conclusion, CYP3A5 genotype and several clinical variables were identified as modulators of the tacrolimus-azole interaction, but these did not permit accurate predictions in individual patients.
Assuntos
Biomarcadores/análise , Interações Medicamentosas , Rejeição de Enxerto/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Tacrolimo/uso terapêutico , Triazóis/uso terapêutico , Voriconazol/uso terapêutico , Antifúngicos/uso terapêutico , Citocromo P-450 CYP3A/genética , Feminino , Seguimentos , Genótipo , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision-making. We collected, air-inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CT examination. Affected target regions were scanned by using micro-CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non-allograft-related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft-related reasons. CT scanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft-related declines. CT and micro-CT examinations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CT abnormalities in other lungs. CT-based measurements showed a higher mass and density in the lungs with CT alterations compared with lungs without CT abnormalities. CT could aid in the decision-making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts.
Assuntos
Tomada de Decisões , Transplante de Pulmão/estatística & dados numéricos , Pulmão/fisiopatologia , Alocação de Recursos , Doadores de Tecidos/provisão & distribuição , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos , Adulto JovemRESUMO
Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS (n = 20) and time-matched stable lung transplant recipients (n = 20). Serial PRM measurements were performed prediagnosis, at time of BOS diagnosis, and postdiagnosis (Tpre , T0 , and Tpost , respectively), or at a postoperatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpre to T0 (p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOS group. This change in PRM continued to Tpost , which was significantly different compared to the stable patients (p = 0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro-CT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate output to monitor BOS progression in lung transplant recipients.
Assuntos
Bronquiolite Obliterante/diagnóstico , Rejeição de Enxerto/diagnóstico , Transplante de Pulmão/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Adulto , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/etiologia , Progressão da Doença , Feminino , Seguimentos , Volume Expiratório Forçado , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SíndromeRESUMO
Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx.
Assuntos
Antibioticoprofilaxia , Azitromicina/uso terapêutico , Bacteriemia/tratamento farmacológico , Bronquiolite Obliterante/cirurgia , Rejeição de Enxerto/tratamento farmacológico , Transplante de Pulmão/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bronquiolite Obliterante/complicações , Estudos de Coortes , Método Duplo-Cego , Feminino , Seguimentos , Volume Expiratório Forçado , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Masculino , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Síndrome , Transplante HomólogoRESUMO
Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with variable biological and clinical behavior. There is increasing experience with liver transplantation (LiTx) for hepatic EHE, even in cases of extrahepatic disease localization. Until now, no cases of lung transplantation (LuTx) had been reported for pulmonary EHE. This report describes three cases of EHE with multifocal disease in patients who underwent either serial or combined LiTx and LuTx.
Assuntos
Hemangioendotelioma Epitelioide/cirurgia , Transplante de Fígado , Transplante de Pulmão , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Chronic rejection remains the most important complication after lung transplantation (LTx). There is mounting evidence that both rheumatoid arthritis and chronic rejection share similar inflammatory mechanisms. As genetic variants in the FCGR2A gene that encodes the immunoglobulin gamma receptor (IgGR) have been identified in rheumatoid arthritis, we investigated the relationship between a genetic variant in the IgGR gene and chronic rejection and mortality after LTx. Recipient DNA from blood or explant lung tissue of 418 LTx recipients was evaluated for the IgGR (rs12746613) polymorphism. Multivariate analysis was carried out, correcting for several co-variants. In total, 216 patients had the CC-genotype (52%), 137 had the CT-genotype (33%) and 65 had the TT-genotype (15%). Univariate analysis demonstrated higher mortality in the TT-genotype compared with both other genotypes (p < 0.0001). Multivariate analysis showed that the TT-genotype had worse survival compared with the CC-genotype (hazard ratio [HR] = 2.26, p = 0.0002) but no significance was observed in the CT-genotype (HR = 1.32, p = 0.18). No difference was seen for chronic rejection. The TT-genotype demonstrated more respiratory infections (total, p = 0.037; per patient, p = 0.0022) compared with the other genotypes. A genetic variant in the IgGR is associated with higher mortality and more respiratory infections, although not with increased prevalence of chronic rejection, after LTx.
Assuntos
Rejeição de Enxerto/genética , Rejeição de Enxerto/mortalidade , Transplante de Pulmão/mortalidade , Polimorfismo Genético/genética , Receptores de IgG/genética , Feminino , Seguimentos , Genótipo , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Infecções Respiratórias/etiologia , Infecções Respiratórias/mortalidade , Fatores de Risco , Taxa de SobrevidaRESUMO
Isolated lung transplantation (LuTx) and liver transplantation are established treatments for irreversible lung and liver failure. Combined liver and lung transplantation (cLiLuTx) is a less common, but approved therapy of combined organ failure, mostly applied in patients suffering from progressive cystic fibrosis and advanced liver disease. We report a patient who was listed for LuTx due to end-stage chronic obstructive pulmonary disease and who developed drug-induced acute hepatic failure. The only therapeutic option was hyper-urgent cLiLuTx. To correct the poor coagulation in order to reduce the per-operative risk of bleeding, the liver was transplanted first. In anticipation of the longer lung preservation time, cold flushed lungs were preserved on a portable lung perfusion device for ex vivo normothermic perfusion for 11 h 15 min, transplanted sequentially off-pump, and reperfused after a total ex vivo time of 13 h 32 min and 16 h for the first and second lung, respectively. Ten months later, the patient is doing well and no rejection occurred. Normothermic ex vivo lung perfusion may help to prolong preservation time, facilitating long-distance transport and combined organ transplantation.
Assuntos
Enfisema/cirurgia , Falência Hepática/cirurgia , Transplante de Fígado , Transplante de Pulmão , Enfisema/complicações , Feminino , Humanos , Falência Hepática/complicações , Pessoa de Meia-IdadeRESUMO
Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+) cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1ß, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1ß/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.
Assuntos
Azitromicina/uso terapêutico , Bronquite/tratamento farmacológico , Rejeição de Enxerto/tratamento farmacológico , Transplante de Pulmão/efeitos adversos , Linfócitos/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Complicações Pós-Operatórias , Adolescente , Adulto , Antibacterianos/uso terapêutico , Bronquite/etiologia , Lavagem Broncoalveolar , Proteína C-Reativa , Citocinas/metabolismo , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Pneumopatias/complicações , Pneumopatias/cirurgia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Prognóstico , Estudos Prospectivos , Testes de Função Respiratória , Estudos Retrospectivos , Espirometria , Transplante Homólogo , Adulto JovemRESUMO
This case report describes the evolution of pulmonary function findings (FVC, FEV1 and TLC) and CT features with pirfenidone treatment for restrictive allograft syndrome following lung transplantation. Furthermore, we herein report hypermetabolic activity on (18) F-FDG PET imaging in this setting, which could indicate active fibroproliferation and pleuroparenchymal remodeling. These findings may warrant further investigation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Enfisema/cirurgia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Fibrose Pulmonar/cirurgia , Piridonas/uso terapêutico , Aloenxertos , Enfisema/complicações , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/etiologia , Fibrose Pulmonar/complicações , Compostos Radiofarmacêuticos , Síndrome , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The effects of exercise training after lung transplantation have not been studied in a randomized controlled trial so far. We investigated whether 3 months of supervised training, initiated immediately after hospital discharge, improve functional recovery and cardiovascular morbidity of patients up to 1 year after lung transplantation. Patients older than 40 years, who experienced an uncomplicated postoperative period, were eligible for this single blind, parallel group study. Sealed envelopes were used to randomly allocate patients to 3 months of exercise training (n = 21) or a control intervention (n = 19). Minutes of daily walking time (primary outcome), physical fitness, quality of life and cardiovascular morbidity were compared between groups adjusting for baseline assessments in a mixed models analysis. After 1 year daily walking time in the treated patients (n = 18) was 85 ± 27 min and in the control group (n = 16) 54 ± 30 min (adjusted difference 26 min [95%CI 8-45 min, p = 0.006]). Quadriceps force (p = 0.001), 6-minute walking distance (p = 0.002) and self-reported physical functioning (p = 0.039) were significantly higher in the intervention group. Average 24 h ambulatory blood pressures were significantly lower in the treated patients (p ≤ 0.01). Based on these results patients should be strongly encouraged to participate in an exercise training intervention after lung transplantation.
Assuntos
Atividades Cotidianas , Exercício Físico , Transplante de Pulmão , HumanosRESUMO
The first vascularized tracheal allotransplantation was performed in 2008. Immunosuppression was stopped after forearm implantation and grafting of the recipient mucosa to the internal site of the transplant. Nine months after forearm implantation, the allograft was transplanted to the tracheal defect on the radial blood vessels. Since then, four additional patients have undergone tracheal allotransplantation, three (patients 2-4) for long-segment stenosis and one (patient 5) for a low-grade chondrosarcoma. Our goal was to reduce the time between forearm implantation and orthotopic transplantation and to determine a protocol for safe withdrawal of immunosuppressive therapy. Following forearm implantation, all transplants became fully revascularized over 2 months. Withdrawal of immunosuppression began 4 months after graft implantation and was completed within 6 weeks in cases 2-4. Repopulation of the mucosal lining by recipient cells, to compensate for the necrosis of the donor mucosa, was not complete. This resulted in partial loss of the allotransplant in patients 2-4. In patient 5, additional measures promoting recipient cell repopulation were made. The trachea may be used as a composite tissue allotransplant after heterotopic revascularization in the forearm. Measures to maximize recipient cell repopulation may be important in maintaining the viability of the transplant after cessation of immunosuppression.
Assuntos
Aprendizagem , Traqueia/transplante , Transplante Homólogo , Adolescente , Feminino , Humanos , Imunossupressores/administração & dosagem , Pessoa de Meia-IdadeRESUMO
Acute rejection represents a major problem after organ transplantation, being a recognized risk for chronic rejection and mortality. Recently, it became clear that lymphocytic bronchiolitis (LB, B-grade acute rejection) is more important than previously thought, as it predisposes to chronic rejection. We aimed to verify whether daily fluctuations of air pollution, measured as particulate matter (PM) are related to histologically proven A-grade rejection and/or LB and bronchoalveolar lavage (BAL) fluid cellularity after lung transplantation. We fitted a mixed model to examine the association between daily variations in PM(10) and A-grade rejection/LB on 1276 bronchoscopic biopsies (397 patients, 416 transplantations) taken between 2001 and 2011. A difference of 10 µg/m(3) in PM(10) 3 days before diagnosis of LB was associated with an OR of 1.15 (95% CI 1.04-1.27; p = 0.0044) but not with A-grade rejection (OR = 1.05; 95% CI 0.95-1.15; p = 0.32). Variations in PM(10) at lag day 3 correlated with neutrophils (p = 0.013), lymphocytes (p = 0.0031) and total cell count (p = 0.024) in BAL. Importantly, we only found an effect of PM10 on LB in patients not taking azithromycin. LB predisposed to chronic rejection (p < 0.0001). The risk for LB after lung transplantation increased with temporal changes in particulate air pollution, and this was associated with BAL neutrophilia and lymphocytosis. Azithromycin was protective against this PM effect.
Assuntos
Poluição do Ar/efeitos adversos , Bronquiolite/etiologia , Transplante de Pulmão/efeitos adversos , Linfócitos/patologia , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Biópsia , Bronquiolite/tratamento farmacológico , Bronquiolite/patologia , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosAssuntos
Transplante de Órgãos , Sarcoidose Pulmonar/cirurgia , Sarcoidose/cirurgia , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/cirurgia , Humanos , Falência Hepática/etiologia , Falência Hepática/cirurgia , Insuficiência Renal/etiologia , Insuficiência Renal/cirurgia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/cirurgia , Sarcoidose/complicações , Sarcoidose Pulmonar/complicações , Taxa de SobrevidaRESUMO
Methemoglobinemia is a rare blood disorder that should be suspected in patients with cyanosis and low oxygen saturation of around 85%, especially when both do not improve despite supplemental oxygen. We describe the case of a 67-year-old lung transplant patient who was treated with primaquine and clindamycin because of a positive Pneumocystis jirovecii polymerase chain reaction on bronchoalveolar lavage fluid. Soon thereafter the patient developed increasing shortness of breath, central cyanosis and hypoxia, with an oxygen saturation of 86% on pulse oximetry despite supplemental oxygen. Arterial blood gas analysis showed a peculiar dark brown color and a significantly increased methemoglobin percentage. A diagnosis of methemoglobinemia due to primaquine was made. As treatment option, we preferred ascorbic acid over methylene blue because of concerns of possibly eliciting a serotonin syndrome. Our patient recovered rapidly after initiation of appropriate treatment. A high index of suspicion is crucial since this condition is potentially fatal.
Assuntos
Aloenxertos , Pulmão , Bronquiolite Obliterante , Humanos , Transplante de Pulmão , Fenótipo , Transplante HomólogoRESUMO
Azithromycin (AZM) improved bronchiolitis obliterans syndrome (BOS) and reduced aspiration in lung transplant (LTx) recipients. We hypothesize that AZM could improve graft and overall survival more efficiently in LTx patients with BOS who have bile acid (BA) aspiration by protecting against the aspiration-induced progression of BOS. The goal was to compare FEV(1) (% baseline), BOS progression and overall survival in LTx recipients treated with AZM for BOS, both with versus without BA aspiration. Therefore, LTx recipients treated with AZM for BOS were recruited and broncho-alveolar lavage (BAL) samples were analyzed for the presence of BA and neutrophilia before the start of AZM treatment. Short-term effect of AZM on FEV(1) and BAL neutrophilia was assessed, progression of BOS and survival were followed-up for 3 years and results were compared between patients with/without BA aspiration. 19/37 LTx patients had BA in BAL. BA aspiration predisposed to a significantly worse outcome, in terms of decline in FEV(1) , progression of BOS ≥ 1 and survival. AZM does not seem to protect against the long-term allograft dysfunction caused by gastroesophageal reflux (GER) and aspiration and an additional treatment targeting aspiration may be indicated in those LTx patients.
Assuntos
Azitromicina/uso terapêutico , Ácidos e Sais Biliares/fisiologia , Bronquiolite Obliterante/tratamento farmacológico , Bronquiolite Obliterante/etiologia , Transplante de Pulmão/efeitos adversos , Aspiração Respiratória/tratamento farmacológico , Aspiração Respiratória/etiologia , Adulto , Antibacterianos/uso terapêutico , Ácidos e Sais Biliares/análise , Bronquiolite Obliterante/fisiopatologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Estudos de Coortes , Progressão da Doença , Feminino , Volume Expiratório Forçado , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Pulmão/mortalidade , Transplante de Pulmão/patologia , Transplante de Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Aspiração Respiratória/fisiopatologiaRESUMO
Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV1) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS. A double-blind randomised controlled trial of azithromycin (n = 40) or placebo (n = 43), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005-2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV1, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV1 with open-label azithromycin. BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p = 0.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092-0.816; p = 0.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV1 (p = 0.028), and lower airway neutrophilia (p = 0.015) and systemic C-reactive protein levels (p = 0.050) over time. Open-label azithromycin for BOS improved FEV1 in 52.2% patients. No serious adverse events were noted. Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV1 and reduces BOS 2 yrs after LTx.
Assuntos
Azitromicina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Pulmão/métodos , Adulto , Bronquiolite Obliterante/prevenção & controle , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Placebos , Modelos de Riscos Proporcionais , Transplante Homólogo , Resultado do TratamentoRESUMO
Lung transplantation is a life-saving treatment option in carefully selected patients with end-stage lung disease. Life expectancy after this form of treatment has progressively increased with a current survival of 90% after 1 year, 70% after 5 years, and 50% after 10 years in experienced centers. Apart from a survival benefit, this treatment aims to improve the quality of life. Bilateral lung transplantation is the type of operation that is performed most frequently because of superior survival results, especially when chronic rejection develops. Single lung transplantation is now reserved for older patients with pulmonary fibrosis. Heart-lung transplantation is rarely done, only in patients with Eisenmenger's syndrome or complex congenital heart disease. Belgium is one of the world leaders in terms of number of deceased organ donors with a lung recovery rate of about 35%. With a total of 8.3 lung transplants per million population, Belgium is currently the number 1 in the world. The procedure nowadays is performed in 4 University Hospitals (UA-KUL-ULB-UCL) in the country. Between 1983 and 2009, nearly 1000 proedures were performed. The most common indication was emphysema, followed by cystic fibrosis, pulmonary fibrosis, pulmonary arterial hypertension, and Eisenmenger's syndrome. Further application of this treatment option is hampered by several problems such as donor organ shortage, primary graft dysfunction, chronic rejection presenting as bronchiolitis obliterans syndrome, and side effect of chronic immunosuppression. In the Laboratory for Experimental Thoracic Surgery and the Laboratory for Pneumology at the Katholieke Universiteit Leuven, intensive research is done by our group looking for new methods to increase the lung donor pool and to prevent and to treat chronic rejection.