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1.
J Diabetes Complications ; 27(3): 219-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23157988

RESUMO

AIMS: To determine if a diagnostic record of poor treatment compliance (medication non-compliance and/or non-attendance at medical appointments) was associated with all-cause mortality in people with type 1 diabetes. METHODS: This is an observational cohort study of data extracted from The Health Improvement Network (THIN) database, comprising data on patients served by over 350 primary care practices in the U.K. Participants were included in the study if they had diagnostic codes indicative of type 1 diabetes. Treatment non-compliance was defined as missing one or more scheduled appointment, or one or more codes indicating medication non-compliance. RESULTS: Of 2946 patients with type 1 diabetes, 867 (29.4%) had a record of either appointment non-attendance or medication non-compliance in the 30 month compliance assessment period. The crude, unadjusted mortality rate for those patients who were treatment non-compliant was 1.462 (95% CI 0.954-2.205). Following adjustment for confounding factors, treatment non-compliance was associated with increased all-cause mortality (HR=1.642; 95% CI 1.055-2.554). CONCLUSIONS: Treatment non-compliance was associated with increased all-cause mortality in patients with type 1 diabetes. Understanding and addressing factors that contribute to patient treatment non-compliance will be important in improving the life expectancy of patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Cooperação do Paciente , Adolescente , Adulto , Agendamento de Consultas , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/tratamento farmacológico , Registros Eletrônicos de Saúde , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Mortalidade , Atenção Primária à Saúde , Reino Unido/epidemiologia , Adulto Jovem
2.
Diabetes Care ; 35(6): 1279-84, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22511257

RESUMO

OBJECTIVE: To assess the association of compliance with treatment (medication and clinic appointments) and all-cause mortality in people with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were extracted from U.K. general practice records and included patients (N = 15,984) who had diagnostic codes indicative of type 2 diabetes or who had received a prescription for an oral antidiabetic agent and were treated with insulin. Records in the 30 months before the index date were inspected for clinical codes (recorded at consultation) indicating medication noncompliance or medical appointment nonattendance. Noncompliance was defined as missing more than one scheduled visit or having at least one provider code for not taking medications as prescribed. Relative survival postindex date was compared by determining progression to all-cause mortality using Cox proportional hazards models. RESULTS: Those identified as clinic nonattenders were more likely to be smokers, younger, have higher HbA(1c), and have more prior primary care contacts and greater morbidity (P < 0.001). Those identified as medication noncompliers were more likely to be women (P = 0.001), smokers (P = 0.014), and have higher HbA(1c), more prior primary care contacts, and greater morbidity (all P < 0.001). After adjustment for confounding factors, medication noncompliance (hazard ratio 1.579 [95% CI 1.167-2.135]), clinic nonattendance of one or two missed appointments (1.163 [1.042-1.299]), and clinic nonattendance of greater than two missed appointments (1.605 [1.356-1.900]) were independent risk factors for all-cause mortality. CONCLUSIONS: Medication noncompliance and clinic nonattendance, assessed during routine care by primary care physicians or their staff, were independently associated with increased all-cause mortality in patients with type 2 diabetes receiving insulin.


Assuntos
Diabetes Mellitus Tipo 2/mortalidade , Dislipidemias/mortalidade , Hipertensão/mortalidade , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco
3.
Immunology ; 132(3): 394-400, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21070236

RESUMO

Up to one in four lung-transplanted patients develop pulmonary infiltrates and impaired oxygenation within the first days after lung transplantation. Known as primary graft dysfunction (PGD), this condition increases mortality significantly. Complex interactions between donor lung and recipient immune system are the suspected cause. We took an integrative, systems-level approach by first exploring whether the recipient's immune response to PGD includes the development of long-lasting autoreactivity. We next explored whether proteins displaying such differential autoreactivity also display differential gene expression in donor lungs that later develop PGD compared with those that did not. We evaluated 39 patients from whom autoantibody profiles were already available for PGD based on chest radiographs and oxygenation data. An additional nine patients were evaluated for PGD based on their medical records and set aside for validation. From two recent donor lung gene expression studies, we reanalysed and paired gene profiles with autoantibody profiles. Primary graft dysfunction can be distinguished by a profile of differentially reactive autoantibodies binding to 17 proteins. Functional analysis showed that 12 of these proteins are part of a protein-protein interaction network (P=3 x 10⁻6) involved in proliferative processes. A nearest centroid classifier assigned correct PGD grades to eight out of the nine patients in the validation cohort (P=0·048). We observed significant positive correlation (r=0·63, P=0·011) between differences in IgM reactivity and differences in gene expression levels. This connection between donor lung gene expression and long-lasting recipient IgM autoantibodies towards a specific set of proteins suggests a mechanism for the development of autoimmunity in PGD.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Perfilação da Expressão Gênica , Transplante de Pulmão/imunologia , Disfunção Primária do Enxerto/imunologia , Adulto , Idoso , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/genética , Doadores de Tecidos
4.
Immunology ; 130(3): 427-35, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20201985

RESUMO

SUMMARY: Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could be differentiated by a profile of autoantibodies binding to 28 proteins or their peptides. The informative autoantibody profile included down-regulation as well as up-regulation of both IgM and IgG specific reactivities. This profile was evaluated for robustness using a panel of six independent test patients. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in chronic rejection leading to OB.


Assuntos
Autoanticorpos/imunologia , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/imunologia , Rejeição de Enxerto/imunologia , Transplante de Pulmão/imunologia , Adulto , Apoptose/fisiologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Pressão Sanguínea/fisiologia , Bronquiolite Obliterante/etiologia , Quimiotaxia/fisiologia , Progressão da Doença , Feminino , Rejeição de Enxerto/complicações , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Redes e Vias Metabólicas/fisiologia , Análise em Microsséries , Pessoa de Meia-Idade , Análise de Componente Principal , Proteínas/imunologia , Proteínas/metabolismo
5.
J Heart Lung Transplant ; 28(9): 888-93, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19716040

RESUMO

BACKGROUND: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1). METHODS: A multivariate survival and competing risk analysis of a large consecutive series of patients (n = 389) from a national center 1992 to 2004. Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and no available lung function measurements (n = 4). RESULTS: The first maximum FEV(1) occurred at a median 183 days post-transplant. Freedom from BOS was 81%, 53%, 38% and 15%, and cumulative incidence of BOS was 18%, 43%, 57% and 77% at 1, 3, 5 and 10 years post-transplantation, respectively. Acute cellular rejection was independently associated with an increased cause-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV(1) was a significant confounder in all survival and competing risk analyses of BOS (p < 0.05). CONCLUSION: Despite early diagnosis and prompt treatment, acute cellular rejection remains an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV(1).


Assuntos
Bronquiolite Obliterante/epidemiologia , Volume Expiratório Forçado , Rejeição de Enxerto/complicações , Transplante de Pulmão/efeitos adversos , Adulto , Bronquiolite Obliterante/mortalidade , Morte , Feminino , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/fisiopatologia , Transplante de Coração-Pulmão/efeitos adversos , Transplante de Coração-Pulmão/patologia , Humanos , Incidência , Pneumopatias/classificação , Pneumopatias/cirurgia , Transplante de Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Sobreviventes , Fatores de Tempo
6.
J Heart Lung Transplant ; 27(10): 1128-34, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18926405

RESUMO

BACKGROUND: Guidelines for the diagnosis and grading of lymphocytic bronchiolitis (LB) have been available for more than a decade, but agreement is lacking concerning the clinical implications of this histologic finding. OBJECTIVES: Study goals were to describe the overall prevalence and incidence of LB in a consecutive cohort of lung transplant recipients and identify risk factors for the onset, frequency, and severity of LB. METHODS: A retrospective analysis was done of 2,697 transbronchial biopsy (TBB) specimens obtained during the first 2 years after transplantation from 299 consecutive patients who underwent transplantation between 1996 and 2006. RESULTS: Full diameter membranous bronchioli were missing in approximately 30% of TBB specimens. The proportion of patients demonstrating LB remained constant during follow-up (trend test, p = 0.2). The cumulative incidence of LB (>or=B2) was 33%, 53%, 62%, and 68% at 1-, 3-, 6-, and 12-months, respectively. Approximately one-quarter and one-half of the patients had a second episode of >or=B2 within 3 months and 2-years of transplantation, respectively. Exposure to LB during the first 2 years after transplantation was independently associated with the frequency and/or severity of acute cellular rejection (p < 0.0001). The choice between anti-thymocyte globulin or daclizumab induction did not alter the overall frequency and/or severity of LB (p = 0.7). LB grade B2 or higher was associated with increased histologic bronchiolitis obliterans (odds ratio, 3.3, 95% confidence interval, 1.5-6.9, p = 0.001). CONCLUSIONS: The frequency and severity of LB was associated with the occurrence and severity of acute cellular rejection.


Assuntos
Bronquiolite/diagnóstico , Bronquiolite/patologia , Rejeição de Enxerto/diagnóstico , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/patologia , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Biomarcadores , Biópsia/estatística & dados numéricos , Índice de Massa Corporal , Bronquiolite/epidemiologia , Bronquiolite/etiologia , Seguimentos , Rejeição de Enxerto/complicações , Humanos , Pneumopatias/classificação , Pneumopatias/cirurgia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo
7.
Transplantation ; 86(6): 811-9, 2008 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-18813106

RESUMO

BACKGROUND: Parenchymal and bronchial inflammatory and fibrotic lesions other than acute cellular rejection (ACR) and lymphocytic bronchiolitis are prevalent; however, the context in which they appear is unknown, and often no specific treatment is instigated. OBJECTIVES: To describe the prevalence, incidence and possible associations between commonly identified inflammatory and fibrotic lesions in the pulmonary allograft. METHODS: Retrospective chart review of all transbronchial biopsies performed within the first 2 years of 299 lung-transplanted patients in the period 1996 to 2006. RESULTS: A total of 2697 biopsies were evaluated corresponding to a mean of 6+/-2 (median 8) completed schedules per patient. Diffuse alveolar damage (DAD) was the second most common histological finding within the first 2 weeks after transplantation. The peak prevalence of bronchiolitis obliterans organizing pneumonia (BOOP) and interstitial pneumonitis occurred at 4 to 6 weeks, and 6 to 12 weeks, respectively. There was a steady increase in the cumulative proportion of patients with fibrosis and bronchiolitis obliterans, at each successive scheduled surveillance time point beyond 3 months posttransplantation. The strongest histological correlations were between ACR and lymphocytic bronchiolitis (OR 5.1, P<0.0001) or interstitial fibrosis (OR 3.2, P<0.0001). Patients with interstitial pneumonitis and pulmonary hemosiderosis were also more likely to demonstrate the finding of interstitial fibrosis (OR 3.0 and 3.7, P<0.0001, respectively). Acute cellular rejection was not associated with DAD, and patients with lymphocytic bronchiolitis were not more likely to demonstrate features of organizing pneumonia (DAD or BOOP). CONCLUSIONS: Histologic findings of ACR, lymphocytic bronchiolitis, BOOP, and interstitial pneumonitis were directly associated with the development of interstitial fibrosis and bronchiolitis obliterans.


Assuntos
Brônquios/patologia , Inflamação/patologia , Transplante de Pulmão/patologia , Biópsia , Líquido da Lavagem Broncoalveolar , Broncoscopia , Pneumonia em Organização Criptogênica/patologia , Feminino , Transplante de Coração-Pulmão/patologia , Humanos , Incidência , Inflamação/epidemiologia , Pneumopatias/classificação , Pneumopatias/cirurgia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/patologia , Estudos Retrospectivos
8.
Transplantation ; 85(4): 547-53, 2008 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-18347533

RESUMO

BACKGROUND: Acute cellular rejection (ACR) is the most consistently reported risk factor for the development of bronchiolitis obliterans syndrome, an important cause of late mortality after lung transplantation. This retrospective study comprised all transbronchial biopsies (TBB) obtained during the first 2 years after transplantation in a consecutive cohort of 299 patients transplanted 1996-2006 (n=2697). METHODS: TBB were aligned to the closest TBB surveillance schedule. RESULTS: Patients completed a mean of 6+/-2 (median 8) TBB schedules. The proportion of patients demonstrating ACR (>or=A2) decreased with increasing time from transplantation from 43% at 2 weeks to 27% at 6 months, and 13% and 4% at 1 and 2 years, respectively (trend test, P<0.0001). There was a significant trend between increased previous occurrence of ACR and increasing subsequent risk of A>or=2 from 1, 3, and 12 months after transplantation (P<0.0001, P=0.0005, and P=0.001, respectively). Multivariate analyses identified interleukin-2-receptor induction with daclizumab versus antithymocyte globulin was independently associated with more frequent/severe ACR (P<0.0001). CONCLUSIONS: Minimal ACR remains prevalent up to 2 years after lung transplantation. Previous occurrence of ACR was associated with an increased risk of subsequent ACR.


Assuntos
Brônquios/patologia , Rejeição de Enxerto/patologia , Transplante de Pulmão/patologia , Doença Aguda , Adulto , Biópsia , Líquido da Lavagem Broncoalveolar , Dinamarca , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Humanos , Incidência , Transplante de Pulmão/mortalidade , Prevalência , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
9.
J Heart Lung Transplant ; 27(3): 329-34, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18342757

RESUMO

BACKGROUND: The objectives of this study were to assess the frequency and severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in patients with recalcitrant pulmonary sarcoidosis. METHODS: This investigation was a single-center, retrospective study of all patients (n = 25) with end-stage pulmonary sarcoidosis referred for lung transplantation. Hemodynamic measurements were evaluated by right-side cardiac catheterization in 24 of 25 patients. Sildenafil treatment for patients with sarcoidosis-associated PH was introduced in April 2004. RESULTS: The study group of 24 patients (16 men, 8 women) had a median age of 45 (range 35 to 58) years, and duration of sarcoidosis of 11 (range 2 to 38) years. Mean pulmonary arterial pressure (MPAP) was median 36 (range 18 to 73) mm Hg. PH (MPAP >25 mm Hg) was present in 19 of 24 patients (79%). Sildenafil was administered to 12 of 13 patients at a dose of 150 (range 75 to 225) mg/day for 4 (range 1 to 12) months. Sildenafil treatment was associated with reductions in MPAP of -8 mm Hg (CI -1 to -15 mm Hg), and PVR -4.9 Wood units (CI -7.2 to -2.6 Wood units). Cardiac output and cardiac index also increased during treatment (p = 0.01, respectively). There were no consistent changes in 6-minute walk distance. CONCLUSIONS: Patients with severe pulmonary sarcoidosis have a high prevalence of PH. Sildenafil treatment was associated with significant improvements in hemodynamic parameters.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Piperazinas/uso terapêutico , Sarcoidose Pulmonar/complicações , Sulfonas/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Purinas/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Citrato de Sildenafila , Resultado do Tratamento
10.
J Heart Lung Transplant ; 26(11): 1127-34, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022078

RESUMO

BACKGROUND: Because bronchiolitis obliterans syndrome (BOS) is defined and graded according to the decline in forced expiratory volume in 1 second (FEV(1)) relative to a maximal baseline value obtained post-transplantation, the criteria discriminates against recipients with lower maximal baseline values (i.e., constitutes a statistical bias). This study describes the effect of transplant procedure on the development of BOS, adjusting for the absolute value of post-transplant baseline FEV(1). METHODS: All patients receiving a cadaveric lung transplant from 1992 to 2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4). RESULTS: Baseline FEV(1) was strongly associated with the freedom from BOS Grade 1, and longer-duration BOS-free survival in univariate and multivariate survival analyses. After adjusting for baseline FEV(1), and recipient-donor gender, bilateral lung transplantation (BLT) was associated with an increase in the cause-specific risk of BOS Grade 1 (hazard ratio [HR] 2.0, confidence interval [CI] 1.2 to 3.1, p = 0.004), and an increase in the cause-specific risk of death/re-transplantation or BOS Grade 1 as a combined end-point (HR 2.3, CI 1.5 to 3.4, p < 0.0001) compared with single-lung transplantation (SLT). In the competing risk regression model adjusting for recipient-donor gender and transplant procedure, only baseline FEV(1) remained independently associated with the cumulative incidence of BOS Grade 1 (p < 0.05); however, BLT recipients were more likely to have death/re-transplantation unrelated to BOS than SLT recipients. CONCLUSIONS: The absolute value of baseline lung function appears to be an important confounder in the analyses of BOS, and should be considered in future risk factor analyses.


Assuntos
Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/fisiopatologia , Volume Expiratório Forçado/fisiologia , Transplante de Coração-Pulmão/efeitos adversos , Transplante de Pulmão/efeitos adversos , Adulto , Feminino , Sobrevivência de Enxerto/fisiologia , Humanos , Pulmão/fisiopatologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco
11.
Nephrol Dial Transplant ; 22(12): 3616-22, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17675330

RESUMO

BACKGROUND: The nephrotoxity of calcineurin inhibitors in lung-transplanted patients is well described, but previous studies have estimated rather than directly measured glomerular filtration rate (GFR). This study describes the decline of measured GFR in a large cohort of lung-transplanted patients from a national centre, and the correlation between measured and calculated GFR. METHODS: All lung-transplanted patients 1992-2004 (n = 390) were included in a longitudinal analysis. Seven patients were excluded due to retransplantation. Pre- and post-transplant parameters included (51)Cr-labelled EDTA clearance (mGFR) and the Cockcroft-Gault calculated clearance (cGFR). Trough cyclosporine levels (C0) and demographic and transplant information were also included in the analysis. RESULTS: A total of 66959 C0 and serum creatinine and 1945 mGFR measurements pertaining to 383 patients were included in the analysis. Pre-transplant mGFR was significantly lower with respect to recipient age over 60 years; and patients with a referral diagnosis of pulmonary hypertension had a lower mGFR and higher baseline serum creatinine levels than patients with emphysematous disease (P < 0.05). There were linear correlations between log(10) mean interval serum creatinine and log(2) mGFR at all time points pre- and post-transplantation (P < 0.0001, Spearman correlation coefficient = -0.81) and between log(2) cGFR and log(2) mGFR (P < 0.0001, Spearman correlation coefficient = 0.81), however, the agreement between mGFR and cGFR was poor (-2.7 +/- 38.6 ml/min). A simplified repeated measure ANOVA model describing post-transplant GFR over time demonstrated a 54% decline in mGFR within the first 6 months post-transplant. Pre-transplant mGFR was an important determinant of 6 month post-transplantation mGFR. Increasing mean C0, body mass index and early acute renal failure were independent risk factors for a more rapid decline in post-transplant mGFR. CONCLUSION: mGFR decreases dramatically during the first 6 months after lung-transplantation. Avoidance of high dose calcineurin inhibition may postpone the onset of post-transplant end-stage renal failure.


Assuntos
Radioisótopos de Cromo/farmacocinética , Ácido Edético/farmacocinética , Taxa de Filtração Glomerular , Transplante de Pulmão , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Heart Lung Transplant ; 26(7): 681-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17613397

RESUMO

BACKGROUND: The objectives of this study were to describe the natural history of bronchiolitis obliterans syndrome (BOS) in a large consecutive series of patients from a national center in accordance with the most recent grading criteria, and to examine the prognosis with respect to onset and severity of BOS. METHODS: All patients receiving a cadaveric lung transplant between 1992 and 2004 were included in the study (n = 389). Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and lack of available lung function measurements (n = 4). RESULTS: The 1-, 3-, 5- and 10-year actuarial survival rates for the entire series were 81%, 67%, 60% and 36%, respectively. The 1-, 3-, 5- and 10-year actuarial freedom from BOS Grade > or = 1 was 81%, 53%, 38% and 15%, respectively. A Cox regression model with BOS grade as a time-dependent covariate was performed in a sub-group of patients surviving at least 3 years (n = 237). Both progression from BOS Grade 1 to 2 and from BOS Grade 2 to 3 were associated with a significant increase in mortality: hazard ratio (HR) = 3.1 (confidence interval [CI] 1.2 to 7.9) and HR = 2.9 (CI 1.6 to 5.3), respectively. The addition of a non-time-dependent covariate to signify early (within 18 months of transplantation) or late (after 18 months) development of BOS was not significant (p = 0.5). CONCLUSIONS: The development and progression of chronic allograft rejection after lung transplantation (BOS Grades 2 and 3) is associated with a 3-fold increase in the risk of death at each stage, irrespective of whether BOS developed early or late.


Assuntos
Bronquiolite Obliterante/etiologia , Transplante de Pulmão/mortalidade , Índice de Gravidade de Doença , Adulto , Bronquiolite Obliterante/patologia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sobreviventes
13.
Scand J Infect Dis ; 39(4): 362-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17454905

RESUMO

We report on a male patient with bronchiectasis secondary to common variable immune deficiency (CVID) receiving lung transplantation. The patient had been diagnosed with CVID many y prior to right-sided single lung transplantation and was receiving appropriate immunoglobulin substitution therapy. He received antithymocyte globulin induction and maintenance triple therapy with cyclosporine, azathioprine and prednisolone. The early post-operative course was complicated by the development of severe acute cellular rejection and organizing pneumonia. Despite immunoglobulin replacement and antifungal prophylaxis and treatment, Aspergillus fumigatus was repeatedly cultured from bronchoalveolar lavage fluid, 18 months after transplantation. The patient died following a protracted period of repeated hospital admissions, 46 months after transplantation. A review of the literature suggests that many CVID patients appear to have had a complicated post-operative course after lung- and other solid-organ transplantation, and highlights the need for the establishment of international registries for transplanted patients with uncommon conditions.


Assuntos
Aspergilose/imunologia , Imunodeficiência de Variável Comum/cirurgia , Pneumopatias Fúngicas/imunologia , Transplante de Pulmão/efeitos adversos , Aspergilose/patologia , Bronquiectasia/etiologia , Imunodeficiência de Variável Comum/complicações , Evolução Fatal , Humanos , Transplante de Pulmão/patologia , Masculino , Pessoa de Meia-Idade
14.
Eur J Cardiothorac Surg ; 31(1): 75-82, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17134909

RESUMO

OBJECTIVE: Primary graft dysfunction (PGD) causes significant mortality and morbidity after lung transplantation. The objectives of the study were to describe the clinical and histological sequelae of PGD. METHODS: Histology of all patients receiving single-lung transplantation 1999-2004 (n=181) was reviewed. PGD was defined as diffuse radiological infiltration of the lung allograft occurring within the first 72h postoperatively. RESULTS: One patient died intra-operatively. PGD was recorded in 63% (n=113) of 180 consecutive transplant recipients. Patients with PGD had a worse 90-day postoperative mortality (14% versus 3%, p=0.03) and 3-year survival (55% versus 77%, p=0.003). Freedom from bronchiolitis obliterans syndrome was similar in both groups. The maximal FEV(1) was significantly lower in patients with PGD, median 54% (quartiles 48-61%) predicted; compared to patients without PGD, median 59% (quartiles 54-69%) predicted (p=0.003). There was a significant linear trend in the decline of maximal FEV(1) with the presence and increasing severity of radiographic infiltrate (p=0.004). During follow-up, patients with PGD were more likely to demonstrate diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (p=0.009 and p=0.01, respectively). Histological findings of diffuse alveolar damage correlated closely with extent of radiological infiltration (p<0.0001). CONCLUSIONS: Transplant recipient survival, lung function, and histological findings of diffuse alveolar damage appear to be closely correlated with the appearance and severity of PGD.


Assuntos
Transplante de Pulmão/efeitos adversos , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/etiologia , Bronquiolite Obliterante/etiologia , Edema/etiologia , Edema/patologia , Feminino , Seguimentos , Volume Expiratório Forçado , Rejeição de Enxerto , Humanos , Pulmão/fisiopatologia , Transplante de Pulmão/métodos , Transplante de Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Prognóstico , Traumatismo por Reperfusão/fisiopatologia , Análise de Sobrevida , Resultado do Tratamento , Capacidade Vital
15.
Scand J Infect Dis ; 38(4): 281-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16715596

RESUMO

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Tipagem e Reações Cruzadas Sanguíneas , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Pulmão , Adolescente , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Heart Lung Transplant ; 25(6): 638-47, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16730569

RESUMO

OBJECTIVE: This study examined the effects of anti-thymocyte globulin (ATG) and daclizumab immunosuppressive induction therapy on the frequency and severity of acute cellular rejection in lung transplantation patients. METHOD: A retrospective analysis was conducted of 335 lung transplantation patients from a single center in the period 1992 to 2003. Patients completed standard ATG (Merieux, 2.5 mg/kg/day, or ATGAM, 12.5 mg/kg/day, for 3 consecutive days) (n = 151) or daclizumab (5 fortnightly treatments at a dose of 1 mg/kg) (n = 151) induction therapy. End points included acute cellular rejection requiring treatment (> or = A2), and moderate/severe acute cellular rejection (A3/A4). RESULTS: The percentage of patients free of rejection requiring treatment (< A2) was 32% at 3 months and 26% at 2 years after transplantation in the ATG group and 9% and 0%, respectively, in the daclizumab group (p < 0.0001). Compared with the ATG group, a significantly higher proportion of patients in the daclizumab group experienced 3 or more episodes of acute cellular rejection > or = A2 during the first 3 months (p < 0.0001) and the entire 2-year follow-up (p < 0.0001). The daclizumab group also experienced more moderate/severe acute cellular rejection episodes compared with the ATG group during the first 3 months (p = 0.005). Cox regression analysis demonstrated ATG induction therapy was independently associated with a significantly longer duration of freedom from acute cellular rejection requiring treatment (> or = A2) (p < 0.001). CONCLUSION: After lung transplantation, ATG induction appears to be superior to daclizumab induction in the reduction in the incidence and severity of acute cellular rejection.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Pulmão/imunologia , Anticorpos Monoclonais Humanizados , Área Sob a Curva , Infecções por Citomegalovirus/epidemiologia , Daclizumabe , Rejeição de Enxerto/epidemiologia , Transplante de Coração-Pulmão/imunologia , Humanos , Incidência , Transtornos Linfoproliferativos/epidemiologia , Reoperação , Estudos Retrospectivos , Sirolimo/uso terapêutico , Análise de Sobrevida
17.
J Heart Lung Transplant ; 24(11): 1834-43, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16297790

RESUMO

OBJECTIVE: To review the 13-year clinical experience of a single center's adult lung transplantation program. METHODS: From January 1992 to December 2003, 369 lung transplantations were performed on 362 patients. Single lung transplantation was performed in 234 cases, double lung transplantation in 113 cases (comprising en-bloc double lung transplantation in 44 cases and bilateral sequential lung transplantation in 69 cases), heart-lung transplantation in 21 cases, and lobe of lung transplantation in 1 case. Recipient diagnoses included chronic obstructive pulmonary disease (COPD) (n = 175), alpha1 antitrypsin (alpha1AT) deficiency (n = 86), cystic fibrosis (n = 36), pulmonary fibrosis (n = 20), Eisenmenger syndrome and secondary pulmonary hypertension (n = 24), primary pulmonary hypertension (n = 8), sarcoidosis (n = 7), silicosis (n = 4), bronchiectasis (n = 1), and graft-vs-host disease (n = 1). RESULTS: For patients surviving to discharge, the median duration of the intensive care unit stay was 3 days (1-67), and the median duration of the post-operative hospital stay was 37 days (16-144). Mortality for the entire series was 6% at 30 days and 10% at 90 days. The main causes of post-operative inpatient death were primary graft failure (41%), sepsis (29%), cardiac (15%), and hemorrhage (9%). The 1-, 3-, 5-, and 10-year actuarial survival rates for the entire series was 81%, 68%, 63%, and 36%, respectively. There were no significant differences in survival between types of transplant. No significant differences in survival were seen between alpha(1)AT deficiency and COPD patients after stratifying for age. Cox regression analysis demonstrated that age 60 years or older, donor age 50 years or older, and a recipient pre-operative body mass index of 25 or higher were independent predictors of poor survival. CONCLUSIONS: This center has 1-, 3-, and 5-year survival rates comparable to other high volume centers. Recipient age, pre-operative body mass index, and donor age significantly influence outcome after lung transplantation.


Assuntos
Transplante de Coração-Pulmão/mortalidade , Pneumopatias/mortalidade , Transplante de Pulmão/mortalidade , Adulto , Fatores Etários , Idoso , Antibioticoprofilaxia , Índice de Massa Corporal , Dinamarca/epidemiologia , Complexo de Eisenmenger/cirurgia , Feminino , Humanos , Hipertensão Pulmonar/cirurgia , Tempo de Internação , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/cirurgia , Fibrose Pulmonar/cirurgia , Estudos Retrospectivos , Sarcoidose Pulmonar/cirurgia , Análise de Sobrevida , Deficiência de alfa 1-Antitripsina/cirurgia
18.
Pediatr Pulmonol ; 39(5): 473-7, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15786441

RESUMO

The co-occurrence of cystic fibrosis (CF) and sarcoidosis is rare. This case report describes a patient with both diseases. A 13-year-old girl with known CF (homozygous delta F508 defect) presented with a sudden decline in lung function. FEV1 decreased from 80% to 64% predicted, and FVC from 90% to 80% predicted. Diffusion capacity for carbon monoxide (D(L)CO) was 92% predicted. There was no history of cough, dyspnea, or reduced exercise tolerance, but she had arthralgia of the knee- and ankle-joints. A chest radiograph and CT scan of the thorax demonstrated pronounced bilateral hilar and mediastinal lymphadenopathy, compatible with pulmonary sarcoidosis. Histological examination of lymph node biopsy specimens obtained at mediastinoscopy demonstrated noncaseating epithelioid-cell granuloma. The majority of lymphocytes were CD4+ T lymphocytes, with a CD4+/CD8+ ratio of 5:1. The patient showed a prompt response to treatment with oral corticosteroids, and lung function returned to baseline levels. Subsequent radiographic appearances showed almost complete regression of mediastinal lymphadenopathy. The probability that CF and sarcoidosis would coexist by chance in a Danish child of this age is approximately 1:10(9). The collective incidence and geographic distribution of previously described patients with coexistent CF and sarcoidosis lend support to an association between the two diseases.


Assuntos
Fibrose Cística/complicações , Sarcoidose Pulmonar/complicações , Adolescente , Anti-Inflamatórios/uso terapêutico , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Glucocorticoides/uso terapêutico , Humanos , Prednisolona/uso terapêutico , Capacidade de Difusão Pulmonar/fisiologia , Capacidade Vital/fisiologia
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