Assuntos
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
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
The single most important cause of late mortality after lung transplantation is chronic lung allograft dysfunction (CLAD). However, the pathological development of CLAD was not as simple as previously presumed and subclassification phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD), have been introduced. We want to re-investigate how CLAD manifests in the murine orthotopic lung transplant model and investigate the role of interleukin 17A (IL-17A) within this model. Orthotopic LTx was performed in CB57BL/6, IL-17 WT and IL-17 KO mice. In a first experiment, CB57BL/6 mice receiving an isograft (CB57BL/6) or allograft (BALB/C) were compared. In a second experiment IL-17 WT and IL-17 KO mice (both CB57BL/6 background) received an allograft (BALB/C). Mice received daily immunosuppression with steroids and cyclosporine and were sacrificed 10weeks after transplantation for histopathological analysis by an experienced lung pathologist. After murine orthotopic lung transplantation, the allograft histopathologically presented features of human rCLAD (i.e. overt inflammation, pleural/parenchymal fibrosis and obliterative bronchiolitis). In the IL-17A KO group, less inflammation in the bronchovascular axis (p=0.03) was observed and a non-significant trend towards less bronchovascular fibrosis, pleural/septal inflammation and fibrosis, and parenchymal inflammation and fibrosis when compared to WT mice. The major mismatch orthotopic lung transplant model resembles features of human rCLAD. IL-17A mediated immunity is involved in the inflammatory component, but had little influence on the degree of fibrosis. Further mechanistic and therapeutic studies in this mouse model are needed to fully understand the mechanisms in rCLAD.
Assuntos
Obstrução das Vias Respiratórias/imunologia , Bronquiolite Obliterante/imunologia , Rejeição de Enxerto/imunologia , Interleucina-17/imunologia , Transplante de Pulmão , Obstrução das Vias Respiratórias/tratamento farmacológico , Animais , Bronquiolite Obliterante/tratamento farmacológico , Doença Crônica , Ciclosporina/uso terapêutico , Modelos Animais de Doenças , Rejeição de Enxerto/tratamento farmacológico , Humanos , Interleucina-17/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esteroides/uso terapêutico , Transplantados , Transplante HomólogoRESUMO
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
There is increasing knowledge that patients can be predisposed to a certain disease by genetic variations in their DNA. Extensive genetic variation has been described in molecules involved in short- and long-term complications after lung transplantation (LTx), such as primary graft dysfunction (PGD), acute rejection, respiratory infection, chronic lung allograft dysfunction (CLAD), and mortality. Several of these studies could not be confirmed or were not reproduced in other cohorts. However, large multicenter prospective studies need to be performed to define the real clinical consequence and significance of genotyping the donor and receptor of a LTx. The current review presents an overview of genetic polymorphisms (SNP) investigating an association with different complications after LTx. Finally, the major drawbacks, clinical relevance, and future perspectives will be discussed.
Assuntos
Rejeição de Enxerto/genética , Pneumopatias/genética , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/genética , Adulto , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Transplante de Pulmão/métodos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doadores de Tecidos , Transplante HomólogoRESUMO
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
BACKGROUND: According to International Society of Heart and Lung Transplantation criteria, high body mass index (BMI; ≥ 30 kg/m(2)) is a relative contraindication for lung transplantation (LT). On the other hand, low BMI may be associated with worse outcome. We investigated the influence of pre-LT BMI on survival after LT in a single-center study. METHODS: Patients were divided according to the World Health Organization criteria into 4 groups: BMI <18.5 kg/m(2) (underweight), BMI 18.5-24.9 kg/m(2) (normal weight), BMI 25-29.9 kg/m(2) (overweight), and BMI ≥ 30 kg/m(2) (obesity). An additional analysis was made per underlying disease. RESULTS: BMI was determined in a cohort of 546 LT recipients, of which 28% had BMI <18.5 kg/m(2). Underweight resulted in similar survival (P = .28) compared with the normal weight group. Significantly higher mortality was found in overweight (P = .016) and obese patients (P = .031) compared with the normal-weight group. Subanalysis of either underweight (P = .19) or obese COPD patients (P = .50) did not reveal worse survival. In patients with interstitial lung disease, obesity was associated with increased mortality (P = .031) compared with the normal-weight group. In cystic fibrosis patients, underweight was not associated with a higher mortality rate (P = .12) compared with the normal-weight group. CONCLUSIONS: Low pre-LT BMI did not influence survival rate in our cohort, independently from underlying disease.
Assuntos
Índice de Massa Corporal , Transplante de Pulmão , Estudos de Coortes , Feminino , Humanos , Pneumopatias/cirurgia , Masculino , Análise Multivariada , Estudos RetrospectivosRESUMO
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
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
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 ProspectivosRESUMO
Most adults are Varicella zoster virus (VZV)-positive at the age of 20 years. Some, however, remain antibody-negative and may develop primary chicken pox during adulthood. We report a patient with Williams-Campbell syndrome who underwent double-lung transplantation while being VZV-negative. One year after the successful procedure, he was admitted with fulminant hepatic failure and some cutaneous vesicles in his face. Despite a rapid diagnosis of VZV infection and treatment with acyclovir, his situation deteriorated within 24 hours and while awaiting an urgent liver transplantation, he developed multiple organ failure and died.
Assuntos
Varicela/virologia , Herpesvirus Humano 3/patogenicidade , Falência Hepática Aguda/etiologia , Transplante de Pulmão/efeitos adversos , Insuficiência Respiratória/cirurgia , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Bronquiectasia/complicações , Varicela/complicações , Varicela/diagnóstico , Varicela/tratamento farmacológico , Varicela/transmissão , Evolução Fatal , Humanos , Transplante de Fígado , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência Respiratória/etiologia , Fatores de Tempo , Listas de EsperaRESUMO
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
BACKGROUND: Pseudomonal airway colonization is a risk factor for chronic allograft dysfunction after lung transplantation (LTx). Pseudomonas aeruginosa exoproteases are involved in initiating colonization, and immune complexes directed against these proteases may activate innate immune responses. OBJECTIVE: To investigate whether specific antibodies against pseudomonal proteases could be measured in bronchoalveolar lavage (BAL) fluid, whether they are associated with innate immune responses, and whether they could identify patients with chronic P. aeruginosa colonization after LTx. MATERIALS AND METHODS: BAL fluid from 40 noncolonized and 25 chronically colonized LTx recipients was retrospectively assayed for IgG antibodies against P. aeruginosa alkaline protease (AP), elastase (Ela), and exotoxin (Exo), and for BAL total and differential cell counts and IL-8 protein concentration. RESULTS: BAL anti-Ela and anti-Exo antibody titers were significantly increased in colonized compared with noncolonized patients (P = .009 and P = .02, respectively), whereas anti-AP titers were comparable (P = .79). Antibody titers strongly correlated with each other, and anti-Ela and anti-Exo titers, but not anti-AP titers, also correlated with BAL total cellularity, neutrophilia, and IL-8 protein concentration. Anti-Ela antibodies demonstrated the greatest diagnostic value in receiver operating characteristic analysis to detect chronic airway colonization (P = .009), followed by anti-Exo (P = .02) and anti-AP (P = .79). A combination of all 3 antibodies resulted in overall sensitivity of 45% (95% confidence interval [CI], 29.3-61.5), specificity of 88% (95% CI, 68.8-97.5), and positive predictive value of 55% (95% CI, 38.5-70.7). CONCLUSION: P. aeruginosa proteases in BAL may be associated with local innate immune responses, and could have the potential to enable detection of chronic colonization after LTx.
Assuntos
Anticorpos Antibacterianos/análise , Líquido da Lavagem Broncoalveolar/imunologia , Transplante de Pulmão , Pseudomonas aeruginosa/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeAssuntos
Enfisema/epidemiologia , Enfisema/cirurgia , Transplante de Pulmão/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: C-reactive protein (CRP), an acute-phase marker of systemic inflammation, may also be a local regulator of the pulmonary immune system. Its role in lung transplantation (LT), however, is unclear. We hypothesized that CRP in bronchoalveolar lavage (BAL) fluid might be associated with airway inflammation or remodeling. Therefore, it could play a role in the development of bronchiolitis obliterans syndrome (BOS). PATIENTS AND METHODS: A total of 100 LT recipients who had undergone transplantation between August 2001 and August 2005 were included in the current cross-sectional study. Patients who were evaluated at 90 days after LT were categorized as either stable (n = 36), colonized (n = 25), or suffering from infection (n = 16) or acute rejection (n = 23). BAL CRP, cell differentials, and interleukin (IL), IL8, transforming growth factor beta (TGFbeta), and vascular endothelial growth factor (VEGF) protein levels, as well as blood leukocytosis, plasma CRP, and forced expiratory value in 1 second (FEV(1); % predicted) were compared between groups. We analyzed the correlation of BAL CRP with inflammatory or remodeling markers and FEV(1). RESULTS: Compared with stable LT recipients, BAL CRP was significantly increased in patients with infection or acute rejection (P < .0001), but not in those with colonization. Generally, BAL CRP levels positively correlated with BAL total cell count, neutrophilia, and IL8 levels, as well as with plasma CRP levels (P < .0001). An inverse correlation was observed with BAL macrophages (P < .01), VEGF (P < .0001), and FEV(1) (P < .0001). Only a trend for a positive, respectively inverse correlation was seen for BAL IL6 and TGFbeta. CONCLUSIONS: The current data corroborate a possible role for CRP in airway inflammation after LT. Its importance for BOS should therefore be further elucidated.
Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Líquido da Lavagem Broncoalveolar/química , Proteína C-Reativa/análise , Inflamação/diagnóstico , Transplante de Pulmão/efeitos adversos , Adulto , Biomarcadores/análise , Estudos Transversais , Feminino , Volume Expiratório Forçado , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Infecções/epidemiologia , Pneumopatias/classificação , Pneumopatias/cirurgia , Transplante de Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
We report the case of a 52-year-old female, who received a left single lung transplantation for end-stage smoking-induced emphysema in 1997. During the last 4 years, she experienced a progressive decline in FEV1, which we attributed to the development of bronchiolitis obliterans syndrome, stage 2. In 2007 she experienced an invasive aspergillosis of the native lung upper lobe, which resolved after 3 months of adequate treatment with voriconazole. After resolution of the infection, both FVC (forced vital capacity) and FEV1 became surprisingly better, due to fibrosis of the affected lobe, compatible with infection-induced volume reduction of the native lung.
Assuntos
Enfisema/cirurgia , Aspergilose Pulmonar Invasiva/complicações , Transplante de Pulmão , Fibrose Pulmonar/microbiologia , Fibrose Pulmonar/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Aspergilose Pulmonar Invasiva/patologia , Pessoa de Meia-Idade , Fibrose Pulmonar/patologia , Capacidade VitalRESUMO
Bronchiolitis obliterans syndrome (BOS) remains a major problem after lung transplantation. Azithromycin seems to be beneficial in some patients with established BOS. We investigated the efficacy of total lymphoid irradiation (TLI) in 6 BOS patients with a continuous decline in FEV(1), despite treatment with azithromycin for a mean of 12 +/- 13 (range, 1-35) months. A historical control group consisted of 5 patients with declining FEV(1), also nonresponders to azithromycin and those not treated with TLI. All 6 TLI patients received the total dose of 8 Gy in 10 sessions. There was a significant change in the decline of the FEV(1) after TLI treatment (from 221 +/- 107 to 94 +/- 79 mL/mo; P = .041). Three patients died, due to BOS progression, overwhelming pneumonia, and sudden cardiac arrest, respectively, 3.5, 11, and 26 months after TLI; two patients underwent retransplantation at 6 and 19 months after TLI, respectively. The sixth patient remains stable in BOS stage 3 after a follow-up period of 24 months. In the control group, there was no significant change in FEV(1) decline (209 +/- 97 mL/mo before versus 193 +/- 81 mL/mo after starting azithromycin; P = not significant). Two patients remain stable in BOS stage 3, 1 died of BOS progression, and the 5th patient is scheduled for retransplantation. We conclude that patients who do not or no longer respond to azithromycin may benefit from TLI, as suggested by a decreased rate in decline of the FEV(1).