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BACKGROUND: Long-term outcomes of lung transplantation (LTx) remain hampered by chronic lung allograft dysfunction (CLAD). Matrix metalloproteinase 9 (MMP-9) is a secretory endopeptidase identified as a key mediator in fibrosis processes associated with CLAD. The objective of this study was to investigate whether plasma MMP9 levels may be prognostic of CLAD development. METHODS: Participants were selected from the Cohort in Lung Transplantation (COLT) for which a biocollection was associated. We considered two time points, year 1 (Y1) and year 2 (Y2) post-transplantation, for plasma MMP-9 measurements. We analysed stable recipients at those time points, comparing those who would develop a CLAD within the 2 years following the measurement to those who would remain stable 2 years after. RESULTS: MMP-9 levels at Y1 were not significantly different between the CLAD and stable groups (230 ng/ml vs. 160 ng/ml, p = 0.4). For the Y2 analysis, 129 recipients were included, of whom 50 developed CLAD within 2 years and 79 remained stable within 2 years. MMP-9 plasma median concentrations were higher in recipients who then developed CLAD than in the stable group (230 ng/ml vs. 118 ng/ml, p = 0.003). In the multivariate analysis, the Y2 MMP-9 level was independently associated with CLAD, with an average increase of 150 ng/ml (95% CI [0-253], p = 0.05) compared to that in the stable group. The Y2 ROC curve revealed a discriminating capacity of blood MMP-9 with an area under the curve of 66%. CONCLUSION: Plasmatic MMP-9 levels measured 2 years after lung transplantation have prognostic value for CLAD.
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Trasplante de Pulmón , Metaloproteinasa 9 de la Matriz , Humanos , Pronóstico , Aloinjertos , Trasplante de Pulmón/efectos adversos , Pulmón , Biomarcadores , Estudios RetrospectivosRESUMEN
BACKGROUND: Antifibrotic agents (AFAs) are now standard-of-care for idiopathic pulmonary fibrosis (IPF). Concerns have arisen about the safety of these drugs in patients undergoing lung transplantation (LTx). METHODS: We performed a multi-centre, nationwide, retrospective, observational study of French IPF patients undergoing LTx between 2011 and 2018 to determine whether maintaining AFAs in the peri-operative period leads to increased bronchial anastomoses issues, delay in skin healing and haemorrhagic complications. We compared the incidence of post-operative complications and the survival of patients according to AFA exposure. RESULTS: Among 205 patients who underwent LTx for IPF during the study period, 58 (28%) had received AFAs within 4 weeks before LTx (AFA group): pirfenidone in 37 (18.0%) and nintedanib in 21 (10.2%). The median duration of AFA treatment before LTx was 13.8 (5.6-24) months. The AFA and control groups did not significantly differ in airway, bleeding or skin healing complications (p = 0.91, p = 0.12 and p = 0.70, respectively). Primary graft dysfunction was less frequent in the AFA than control group (26% vs. 43%, p = 0.02), and the 90-day mortality was lower (7% vs. 18%, p = 0.046). CONCLUSIONS: AFA therapy did not increase airway, bleeding or wound post-operative complications after LTx and could be associated with reduced rates of primary graft dysfunction and 90-day mortality.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Antifibróticos , Estudios Retrospectivos , Disfunción Primaria del Injerto/tratamiento farmacológico , Disfunción Primaria del Injerto/etiología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Piridonas/efectos adversos , Resultado del TratamientoRESUMEN
Carriers of germline telomerase-related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46-59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow-up of 26 months (IQR 15-46), 38 patients received LT. The overall post-LT median survival was 3.75 years (IQR 1.8-NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5-11.5]) or short telomere (HR 2.2 [1.0-5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Telomerasa , Humanos , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Telomerasa/genéticaRESUMEN
In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM-ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46-59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high-priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow-up (median, 33 [7-63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher-intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM-ILD was similar to that in international all-cause-transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all-cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease.
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Enfermedades Pulmonares Intersticiales , Trasplante de Pulmón , Miositis , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Miositis/cirugía , Miositis/complicaciones , Enfermedades Pulmonares Intersticiales/cirugía , Enfermedades Pulmonares Intersticiales/etiología , Trasplante de Pulmón/efectos adversosRESUMEN
INTRODUCTION: Patients with short telomere-related interstitial lung disease (ILD) have worse outcomes after lung transplantation. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD lung transplant population. METHODS: We conducted a multi-institutional (Brigham and Women's Hospital, Groupe de Transplantation de la SPLF) retrospective cohort study of 63 recipients between 2009 and 2019 with ILD and short telomeres, compared to 4359 recipients from the Scientific Registry of Transplant Recipients with ILD and no known telomeropathy. RESULTS: In the short telomere cohort, six recipients (9.5%) developed dehiscence and nine recipients (14.3%) developed stenosis, compared to 60 (1.4%) and 149 (3.4%) in the control, respectively. After adjusting for age, sex, and bilaterality, the presence of short telomeres was associated with higher odds of dehiscence (odds ratio (OR) = 8.24, 95% confidence interval (CI) = 3.34 20.29, p < .001) and stenosis (OR = 4.63, 95% CI 2.21 9.69, p < .001). CONCLUSION: The association between the presence of short telomeres and post-transplant dehiscence and stenosis suggest that airway complications may be a contributor to increased morbidity and mortality in patients with telomere-related ILD.
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Enfermedades Pulmonares Intersticiales , Trasplante de Pulmón , Constricción Patológica/complicaciones , Femenino , Humanos , Pulmón , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/cirugía , Trasplante de Pulmón/efectos adversos , Estudios Retrospectivos , Telómero/genética , Receptores de TrasplantesRESUMEN
Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.
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Antihipertensivos/uso terapéutico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/mortalidad , Administración Oral , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Drugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation (S aO2 ) in some patients. The present retrospective study of the French Pulmonary Hypertension Registry aimed to describe the clinical characteristics and outcomes of patients showing a ≥3% decrease in S aO2 while treated with PAH drugs. METHODS: We reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement. RESULTS: 173 (24%) patients had a ≥3% decrease in S aO2 . At diagnosis, they were older with a lower diffusing capacity of the lung for carbon monoxide and a shorter 6-min walk distance compared with those who did not display a ≥3% decrease in S aO2 . The percentage of patients meeting the European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease in S aO2 and more patients started long-term oxygen therapy in this group (16% versus 5%; p<0.001). A ≥3% decrease in S aO2 was associated with a poorer survival (hazard ratio 1.81, 95% CI 1.43-2.34; p<0.0001). In a multivariate Cox analysis, a ≥3% decrease in S aO2 was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up. CONCLUSIONS: When treated with PAH drugs, a large subset of patients experience a ≥3% decrease in S aO2 , which is associated with worse long-term outcomes and reduced survival.
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Preparaciones Farmacéuticas , Hipertensión Arterial Pulmonar , Hipertensión Pulmonar Primaria Familiar , Humanos , Oxihemoglobinas , Estudios RetrospectivosRESUMEN
STUDY QUESTION: In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation. PATIENTS AND METHODS: We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres. RESULTS: Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59)â years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5â years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications. ANSWER TO THE STUDY QUESTION: Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.
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Trasplante de Pulmón , Sarcoidosis Pulmonar , Sarcoidosis , Anciano , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Sarcoidosis/cirugía , Sarcoidosis Pulmonar/cirugíaRESUMEN
Bronchiolitis obliterans syndrome is the main limitation for long-term survival after lung transplantation. Some specific B cell populations are associated with long-term graft acceptance. We aimed to monitor the B cell profile during early development of bronchiolitis obliterans syndrome after lung transplantation. The B cell longitudinal profile was analyzed in peripheral blood mononuclear cells from patients with bronchiolitis obliterans syndrome and patients who remained stable over 3 years of follow-up. CD24hi CD38hi transitional B cells were increased in stable patients only, and reached a peak 24 months after transplantation, whereas they remained unchanged in patients who developed a bronchiolitis obliterans syndrome. These CD24hi CD38hi transitional B cells specifically secrete IL-10 and express CD9. Thus, patients with a total CD9+ B cell frequency below 6.6% displayed significantly higher incidence of bronchiolitis obliterans syndrome (AUC = 0.836, PPV = 0.75, NPV = 1). These data are the first to associate IL-10-secreting CD24hi CD38hi transitional B cells expressing CD9 with better allograft outcome in lung transplant recipients. CD9-expressing B cells appear as a contributor to a favorable environment essential for the maintenance of long-term stable graft function and as a new predictive biomarker of bronchiolitis obliterans syndrome-free survival.
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Linfocitos B/metabolismo , Biomarcadores/metabolismo , Bronquiolitis Obliterante/diagnóstico , Rechazo de Injerto/diagnóstico , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Tetraspanina 29/metabolismo , Adolescente , Adulto , Anciano , Bronquiolitis Obliterante/etiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Síndrome , Trasplante Homólogo , Adulto JovenRESUMEN
An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6â months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12â months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1â s (FEV1) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5â µg·m-3 of PM10; -0.75%, 95% CI -1.38--0.12 for 2â µg·m-3 of PM2.5 and -2.58%, 95% CI -4.63--0.53 for 10â µg·m-3 of NO2). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM10 was associated with lower FEV1Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides.
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Contaminación del Aire/efectos adversos , Trasplante de Pulmón , Pulmón/fisiopatología , Material Particulado/análisis , Disfunción Primaria del Injerto/fisiopatología , Adolescente , Adulto , Anciano , Aloinjertos , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/fisiopatología , Enfermedad Crónica , Exposición a Riesgos Ambientales , Femenino , Volumen Espiratorio Forzado , Francia , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Dióxido de Nitrógeno/análisis , Ozono/análisis , Espirometría , Capacidad Vital , Adulto JovenRESUMEN
JSRV (Jaagsiekte Sheep Retrovirus) is a retrovirus inducing a transmissible lung adenocarcinoma in sheep and goats with predominantly lepidic and papillary lesions. This naturally occurring lung cancer in large animals shares many features with human pneumonic-type lung adenocarcinomas with predominant lepidic growth. The metastatic spread is rare in both human and animal cancers. This unique feature prompted us to decipher the angiogenesis pathway in these cancers. We focused on the levels of mRNA and proteins of genes implicated in the extension of JSRV-induced lung adenocarcinomas by studying their expression in lung cancers (n = 10) and normal lungs (n = 10) and in primary epithelial alveolar type II cells derived from cancers (n = 10) or normal lungs (n = 6). In parallel, we evaluated the levels of expression of key genes in lung tissues collected from lepidic (n = 13) or papillary (n = 5) human adenocarcinomas and, when available, adjacent normal lungs (n = 11). We measured the expression of the same key genes implicated in angiogenesis, lymphangiogenesis and degradation of the extracellular matrix. In ovine adenocarcinomas, VEGFR2 and VEGFD mRNA were downregulated in cancers; MMP9, TIMP1 and FGFR2 mRNA were overexpressed as compared to normal lungs. Importantly, VEGFA and VEGFR2 proteins were not expressed in JSRV-induced cancers. In human lepidic adenocarcinomas, VEGFA and VEGFR2 mRNA were weakly expressed and no VEGFR2 protein was detectable. Downregulation of key angiogenic players may contribute to the control of extra thoracic invasion of cancer cells in human and ovine pneumonic-type adenocarcinoma with predominant lepidic growth.
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Adenocarcinoma/genética , Regulación Neoplásica de la Expresión Génica , Retrovirus Ovino Jaagsiekte/fisiología , Neoplasias Pulmonares/genética , Neovascularización Patológica/genética , Neovascularización Patológica/veterinaria , Adenomatosis Pulmonar Ovina/genética , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Pulmón/fisiopatología , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Adenomatosis Pulmonar Ovina/metabolismo , OvinosRESUMEN
BACKGROUND: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation. OBJECTIVES: We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications. METHODS: We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors). RESULTS: Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized. CONCLUSIONS: About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication.
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Anticoagulantes/farmacocinética , Hipertensión Pulmonar/metabolismo , Vitamina K/antagonistas & inhibidores , Administración Oral , Anticoagulantes/administración & dosificación , Disponibilidad Biológica , Creatinina/metabolismo , Femenino , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Trombosis , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a "smoker-like" somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.
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Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Tirosina Quinasas Receptoras/genética , Contaminación por Humo de Tabaco , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Anciano , Quinasa de Linfoma Anaplásico , Biomarcadores , Fosfatidilinositol 3-Quinasa Clase I , Femenino , Francia , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Fosfatidilinositol 3-Quinasas/genética , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Receptor ErbB-2/genética , Fumar , Encuestas y CuestionariosRESUMEN
Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6â months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6â months after initiation of therapy (n=78). After a median follow-up of 4.1â years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6â months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6â months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension.
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Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Adulto , Anciano , Angiografía , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Volumen Sistólico , Resultado del Tratamiento , Disfunción Ventricular Derecha/fisiopatologíaAsunto(s)
Infección Hospitalaria , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Antituberculosos , Genotipo , HumanosRESUMEN
The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.
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Indicadores de Salud , Calidad de Vida , Deficiencia de alfa 1-Antitripsina , Adulto , Anciano , Anciano de 80 o más Años , Bronquitis Crónica/etiología , Progresión de la Enfermedad , Disnea/etiología , Femenino , Estudios de Seguimiento , Francia , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Enfisema Pulmonar/etiología , Sistema de Registros , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/fisiopatología , Deficiencia de alfa 1-Antitripsina/psicologíaRESUMEN
The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD. We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency. 20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7-94.3%) at 3 years and 76.0% (72.9-79.1%) at 5 years. The 3-year survival was 97.4% (96.6-98.2%), 98.0% (96.7-99.3%), 87.7% (84.5-90.9%) and 75.3% (66.0-84.6%) for patients with BODE index 0-2, 3-4, 5-6 and 7-10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival. The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.
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Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Índice de Severidad de la Enfermedad , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/diagnóstico , Adulto , Anciano , Área Bajo la Curva , Calibración , Enfisema/complicaciones , Enfisema/diagnóstico , Enfisema/mortalidad , Femenino , Francia , Humanos , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Probabilidad , Pronóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Curva ROC , Programas Informáticos , Resultado del Tratamiento , Deficiencia de alfa 1-Antitripsina/mortalidadRESUMEN
Alpha-1 antitrypsin deficiency is a frequent genetic disorder associated with pulmonary emphysema in smokers and with liver cirrhosis. Aside from lung or liver transplantation, only replacement therapy can currently slow the progression of emphysema. Progress in the pathogenesis of this disorder (protein misfolding, RER aggregation) is opening the way to new strategies such as proteostasis control. Alpha-1 antitrypsin deficiency remains poorly known and underdiagnosed.
Asunto(s)
Deficiencia de alfa 1-Antitripsina , Alelos , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Humanos , Cirrosis Hepática/etiología , Pliegue de Proteína , Enfisema Pulmonar/etiología , Serpinas/química , Serpinas/fisiología , alfa 1-Antitripsina/química , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/uso terapéutico , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/tratamiento farmacológico , Deficiencia de alfa 1-Antitripsina/epidemiología , Deficiencia de alfa 1-Antitripsina/genéticaRESUMEN
Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).