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1.
N Engl J Med ; 379(23): 2209-2219, 2018 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-30345907

RESUMEN

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).


Asunto(s)
Artritis Reumatoide/genética , Mutación con Ganancia de Función , Enfermedades Pulmonares Intersticiales/genética , Mucina 5B/genética , Anciano , Artritis Reumatoide/complicaciones , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Fibrosis Pulmonar Idiopática/genética , Pulmón/química , Pulmón/patología , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Persona de Mediana Edad , Mucina 5B/análisis , Oportunidad Relativa , Regiones Promotoras Genéticas
2.
Eur Respir J ; 57(2)2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32646919

RESUMEN

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Humanos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Metotrexato/efectos adversos
3.
Int Arch Allergy Immunol ; 182(3): 182-189, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32961531

RESUMEN

INTRODUCTION: Among allergic rhinitis (AR) symptoms, nasal obstruction particularly affects the quality of life. Antihistamines and intranasal corticosteroids are the most frequently prescribed symptomatic drugs, but their efficacy is often incomplete. Essential oils (EO) have shown an anti-inflammatory effect and potential in treating patients with AR. The aim of this study was to evaluate the effectiveness of a hypertonic EO-based nasal spray on perennial AR (PAR) symptoms. METHODS: This prospective, open-label, non-randomized, multicentric trial included 43 patients with PAR sensitized to mites, not controlled for more than a year. All were treated with Puressentiel® Respiratory-Decongestant Nasal Spray for 30 days. Their usual treatment remained unchanged during the study period. Before and after treatment, each participant filled out a rhinitis questionnaire, the Allergic Rhinitis Control Test (ARCT). A nasal inspiratory peak flow (NIPF) was performed. RESULTS: The mean ARCT was 16.4 and 20.5 at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 4.1 (p < 0.001). The proportion of patients with controlled rhinitis after 30 days of treatment was 69.8 versus 14% before treatment (p < 0.001). The mean NIPF was 86.5 L/min and 105.1 L/min at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 18.5 L/min. CONCLUSION: A hypertonic EO-based nasal spray could be a new and natural option in the management of PAR. It could also be used as an add-on therapy when nasal symptoms are not fully controlled.


Asunto(s)
Antialérgicos/administración & dosificación , Aceites Volátiles/administración & dosificación , Rinitis Alérgica Perenne/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rociadores Nasales , Estudios Prospectivos , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/inmunología , Evaluación de Síntomas , Resultado del Tratamiento , Adulto Joven
4.
BMC Infect Dis ; 20(1): 176, 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32093612

RESUMEN

BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Trasplante de Pulmón , Infecciones del Sistema Respiratorio/diagnóstico , Virosis/diagnóstico , Femenino , Volumen Espiratorio Forzado , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Picornaviridae/aislamiento & purificación , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología
5.
Eur Respir J ; 54(5)2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31601709

RESUMEN

INTRODUCTION: Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database. METHODS: All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models. RESULTS: During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT. CONCLUSIONS: This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics.


Asunto(s)
Trasplante de Pulmón/mortalidad , Selección de Paciente , Obtención de Tejidos y Órganos , Adulto , Tratamiento de Urgencia , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Resultado del Tratamiento
6.
J Asthma ; 56(8): 853-860, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29985684

RESUMEN

Background: Essential oils are volatile compounds of plant origin increasingly used by allergic and/or asthmatic subjects to purify indoor air. The active compounds of essential oils belong to terpenes, the most widespread biogenic volatile organic compounds (VOC). Although there is substantial literature showing associations between exposure to chemical VOCs and asthmatic symptoms and impaired respiratory function, the impact of essential oils in patients with asthma has never been studied. Objectives: To evaluate the safety of a purifying air spray containing 41 essential oils (PPAS) in patients with mild or moderate allergic asthma. Methods: This was a prospective open study in which 25 mild (19) and moderate (6) asthmatics were exposed to PPAS, one spray twice a day at 8 am and 8 pm in two different corners of a given subjects bedroom for 4 weeks. Before and after 4 weeks of exposure, fractional exhaled nitric oxide (FeNO), lung function and methacholine challenge (PD20) were performed and asthma control was assessed by the 5 questions of the Asthma Control Test (ACT). The spray was weighed after the 4-week exposure to assess compliance. Results: FeNO was the primary endpoint and was thus analyzed in all (N = 25) subjects irrespective of the level of airflow obstruction. The results apply to all (N = 25) subjects in which FeNO could be measured at D1 and D30 (17 subjects). Mean (SD) FeNO amounted to 37.4 (16.6) and to 33.1 (18.7) ppm before and after PPAS exposure, respectively (p = 0.09). No significant change in lung function and methacholine responsiveness was noted after PPAS exposure, the mean PD20 amounting to 1179 (1124.42) µg (range 100-3200) before and to 1226 (1189.8) µg (p = 0.06) after. The mean ACT before and after PPAS exposure amounted to 20.9 (4.2) and 21 (5.15), respectively (p = 0.80). The mean weight of the PPAS bottles was 211.4 g (DS:0) before the first use and 171.41 g (DS: 29.8) at the end of the study. The average amount of PPAS used was 40.0 g (29.8). In the subgroup of subjects who used the highest quantities of essential oils (>40 g), as assessed by the mean weight of the bottle at the end of the study, FeNO after 30 days of exposure decreased more than in the entire group: 7.9 ppm vs 4.2 ppm (p = 0.07). Conclusion: No difference was noted on airway inflammation, lung function or asthma control in mild and moderate allergic asthmatics after exposure twice a day for one month, to a spray containing a mixture of 41 essential oils.


Asunto(s)
Asma/diagnóstico , Hiperreactividad Bronquial/fisiopatología , Aceites Volátiles/administración & dosificación , Adulto , Anciano , Pruebas Respiratorias , Pruebas de Provocación Bronquial/métodos , Estudios de Cohortes , Espiración/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/análisis , Seguridad del Paciente , Estudios Prospectivos , Pruebas de Función Respiratoria , Sensibilidad y Especificidad , Adulto Joven
7.
Thorax ; 73(3): 283-285, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28724638

RESUMEN

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.


Asunto(s)
Volumen Espiratorio Forzado/fisiología , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/genética , Fumar/efectos adversos , Telómero/metabolismo , Adulto , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/genética , Francia , Encuestas Epidemiológicas , Humanos , Leucocitos , Estudios Longitudinales , Masculino , Factores de Riesgo , Espirometría/métodos , Homeostasis del Telómero , Acortamiento del Telómero , Adulto Joven
8.
Eur Respir J ; 52(2)2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29976654

RESUMEN

Presence of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with poor outcome after lung transplantation. Currently, DSAs are detected using the Luminex technique, which may be overly sensitive. The new C1q assay allows for the exclusive detection of complement (C1q)-binding antibodies, involved in antibody-mediated rejection. We investigated whether early detection of complement-binding DSAs is associated with chronic lung allograft dysfunction (CLAD) and survival.From 2009 to 2012, lung transplant recipients from three transplantation centres were screened for the presence of DSA and their complement-binding capacity during the 6-12 months post-transplantation in a stable condition.The analysis included 168 patients. The 3-year rates of freedom from CLAD and graft survival were lower for patients with complement-binding DSAs (33.6% and 53.7%, respectively), as compared with patients with non-complement-binding DSAs (61.9% and 77.4%, respectively) and patients without DSA (70% and 84.9%, respectively) (p<0.001 and p=0.001, respectively). Detection of complement-binding DSA was associated with a risk of graft loss that was nearly tripled after adjustment for clinical, functional, histological and immunological factors (hazard ratio 2.98, 95% CI 1.33-6.66; p=0.008).Assessment of the C1q-binding capacity of DSA appears to be useful in identifying stable lung transplant recipients at high risk of lung allograft loss.


Asunto(s)
Complemento C1q/inmunología , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Trasplante de Pulmón , Donantes de Tejidos , Adulto , Aloinjertos , Femenino , Francia , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo
9.
J Cardiothorac Vasc Anesth ; 32(4): 1731-1735, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29203299

RESUMEN

OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by the PiCCO2 device to assess cardiac index and pulmonary edema during the postoperative course after single-lung transplantation. DESIGN: Prospective observational study. SETTINGS: Intensive care unit, university hospital (single center). PARTICIPANTS: Single-lung transplant patients. INTERVENTIONS: The authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter and assessed pulmonary edema using extravascular lung water index and pulmonary vascular permeability index measured by PiCCO2. MEASUREMENTS AND MAIN RESULTS: A Bland-Altman method was used to compare cardiac index measured by PiCCO2 and pulmonary artery catheter. Extravascular lung water index and pulmonary vascular permeability index were compared according to the PaO2/FiO2 ratio with a threshold value of 150 mmHg. Ten single-lung transplant patients were included. Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2 (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (-0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water index was higher in the group of PaO2/FiO2 ratio ≤150 mmHg compared with the group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06). CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared with pulmonary artery catheter. However, it might be useful to assess pulmonary edema in acute respiratory failure after single-lung transplantation.


Asunto(s)
Gasto Cardíaco/fisiología , Cateterismo Periférico/tendencias , Agua Pulmonar Extravascular/fisiología , Trasplante de Pulmón/tendencias , Pulmón/fisiología , Cateterismo Periférico/métodos , Femenino , Humanos , Pulmón/irrigación sanguínea , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Termodilución/métodos
10.
J Allergy Clin Immunol ; 139(4): 1176-1185, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27609656

RESUMEN

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. OBJECTIVE: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. METHODS: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. RESULTS: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 µm [25th-75th IQR, 4.0-4.7 µm] and 3.9 µm [25th-75th IQR, 3.7-4.6 µm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. CONCLUSION: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.


Asunto(s)
Asma/terapia , Hipertermia Inducida/métodos , Adulto , Anciano , Asma/patología , Bronquios/patología , Bronquios/efectos de la radiación , Broncoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Pruebas de Función Respiratoria , Resultado del Tratamiento
11.
Eur Respir J ; 50(2)2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28838976

RESUMEN

The COhort of BRonchial obstruction and Asthma (COBRA) is a longitudinal cohort that involves 12 French academic institutions. DNA, serum samples and clinical data are collected at entry and every 6 months thereafter.Of 1080 patients with asthma recruited between 2007 and 2015, 401 had mild/moderate and 613 had severe asthma. In cross-sectional analyses, compared with patients with milder disease, patients with severe asthma had more symptoms, exacerbations, hospitalisations and visits to the emergency department during the preceding 12 months, higher numbers of blood eosinophils, and more comorbidities. More than 60% of patients with severe asthma were therapy-uncontrolled at entry, and 152 of them were being treated with omalizumab. In addition, patients with asthma who had the highest eosinophilia levels (>300/mm3) had shorter asthma duration, lower lung function, and higher rates of severe exacerbations and unacceptable asthma control than patients with lower eosinophil counts.Longitudinal analyses performed in 427 patients with asthma with at least three differential blood cell counts demonstrated that both eosinophil numbers and eosinophil increase over time were associated with the number of exacerbations occurring until the next visit and with Juniper score.Studies with the COBRA cohort will help to improve knowledge concerning the risk and biological factors associated with asthma severity and to better understand their influence on the disease trajectory.


Asunto(s)
Asma , Eosinofilia , Omalizumab/uso terapéutico , Adulto , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/epidemiología , Asma/fisiopatología , Asma/terapia , Estudios de Cohortes , Estudios Transversales , Progresión de la Enfermedad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Eosinofilia/diagnóstico , Eosinofilia/etiología , Femenino , Francia/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria/métodos
12.
Eur Respir J ; 49(3)2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28298402

RESUMEN

Bronchial thermoplasty (BT) is a recent, promising and well-tolerated technique for the treatment of severe asthma. By delivering thermal energy to the airway wall, this procedure can induce early pulmonary opacities seen on computed tomography (CT). We aimed to examine early CT modifications induced by BT and to determine their association with respiratory symptoms.Unenhanced chest CT was performed the day after each BT session in 13 patients with severe asthma, leading to the examination of 38 treated lobes. A total of 15 BT-treated lobes were evaluated in 11 patients at 1 month. The first two patients also underwent CT at 1 week.No symptoms suggestive of pulmonary infection were noted following BT in any patient. Peribronchial consolidations and ground-glass opacities were observed in all treated lobes on day 1, with three lower lobes showing complete collapse. Mild involvement of an adjacent untreated lobe was observed in 12 out of 38 (32%) cases. Opacities had decreased in 5 out of 15 (33%) and disappeared in 10 out of 15 (67%) at 1 month.BT induced early pulmonary peribronchial hyperdensities in all treated lobes. These alterations were unrelated to clinical symptoms and spontaneously decreased or disappeared after 1 month.


Asunto(s)
Asma/diagnóstico por imagen , Asma/cirugía , Bronquios/cirugía , Termoplastia Bronquial , Adulto , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X
13.
Eur Respir J ; 50(5)2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29191952

RESUMEN

α1-antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The pulmonary emphysema in AATD is strongly linked to smoking, but even a proportion of never-smokers develop progressive lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment.The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomised clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD.As AATD is a rare disease, it is crucial to organise national and international registries and collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed.


Asunto(s)
Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/terapia , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/terapia , Adulto , Comités Consultivos , Europa (Continente) , Pruebas Genéticas , Humanos , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Fumar/efectos adversos , Sociedades Médicas
14.
Eur Respir J ; 49(5)2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28495692

RESUMEN

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10-4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10-2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.


Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Enfermedades Pulmonares Intersticiales/genética , Fibrosis Pulmonar/genética , Adulto , Anciano , Artritis Reumatoide/complicaciones , Estudios de Casos y Controles , ADN Helicasas/genética , Europa (Continente) , Exoma , Femenino , Estudios de Asociación Genética , Heterocigoto , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Fibrosis Pulmonar/complicaciones , Factores de Riesgo , Análisis de Secuencia de ADN , Programas Informáticos , Telomerasa/genética
15.
Respir Res ; 18(1): 74, 2017 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-28449678

RESUMEN

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by an unpredictable course. Prognostic markers and disease activity markers are needed. The purpose of this single-center retrospective study was to evaluate the prognostic value of lung fluorodeoxyglucose ([18F]-FDG) uptake assessed by standardized uptake value (SUV), metabolic lung volume (MLV) and total lesion glycolysis (TLG) in patients with IPF. METHODS: We included 27 IPF patients (IPF group) and 15 patients with a gastrointestinal neuroendocrine tumor without thoracic involvement (control group). We quantified lung SUV mean and SUV max, MLV and TLG and assessed clinical data, high-resolution CT (HRCT) fibrosis and ground-glass score; lung function; gender, age, physiology (GAP) stage at inclusion and during follow-up; and survival. RESULTS: Lung SUV mean and SUV max were higher in IPF patients than controls (p <0.00001). For patients with IPF, SUV mean, SUV max, MLV and TLG were correlated with severity of lung involvement as measured by a decline in forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) and increased GAP score. In a univariate and in a multivariate Cox proportional-hazards model, risk of death was increased although not significantly with high SUV mean. On univariate analysis, risk of death was significantly associated with high TLG and MLV, which disappeared after adjustment functional variables or GAP index. Increased MLV and TLG were independent predictors of death or disease progression during the 12 months after PET scan completion (for every 100-point increase in TLG, hazard ratio [HR]: 1.11 (95% CI 1.06; 1.36), p = 0.003; for every 100-point increase in MLV, HR: 1.20 (1.04; 1.19), p = 0.002). On multivariable analysis including TLG or MLV with age, FVC, and DLCO or GAP index, TLG and MLV remained associated with progression-free survival (HR: 1.1 [1.03; 1.22], p = 0.01; and 1.13 [1.0; 1.2], p = 0.005). CONCLUSION: FDG lung uptake may be a marker of IPF severity and predict progression-free survival for patients with IPF.


Asunto(s)
Fluorodesoxiglucosa F18 , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/mortalidad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/estadística & datos numéricos , Fumar/mortalidad , Comorbilidad , Supervivencia sin Enfermedad , Francia/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Pronóstico , Radiofármacos , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Tasa de Supervivencia
16.
J Allergy Clin Immunol ; 138(3): 729-739.e11, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27001157

RESUMEN

BACKGROUND: Asthma is a complex disease with heterogeneous features of airway inflammation and remodeling. The increase in airway smooth muscle (ASM) mass is an essential component of airway remodeling in patients with severe asthma, yet the pathobiological mechanisms and clinical outcomes associated with ASM enlargement remain elusive. OBJECTIVE: We sought to compare ASM area in control subjects and patients with mild-to-moderate or severe asthma and to identify specific clinical and pathobiological characteristics associated with ASM enlargement. METHODS: Bronchial biopsy specimens from 12 control subjects, 24 patients with mild-to-moderate asthma, and 105 patients with severe asthma were analyzed for ASM area, basement membrane thickness, vessels, eosinophils, neutrophils, T lymphocytes, mast cells, and protease-activated receptor 2 (PAR-2). In parallel, the levels of several ASM mitogenic factors, including the PAR-2 ligands, mast cell tryptase, trypsin, tissue factor, and kallikrein (KLK) 5 and KLK14, were assessed in bronchoalveolar lavage fluid. Data were correlated with asthma severity and control both at inclusion and after 12 to 18 months of optimal management and therapy. RESULTS: Analyses across ASM quartiles in patients with severe asthma demonstrated that patients with the highest ASM quartile (median value of ASM area, 26.3%) were younger (42.5 vs ≥50 years old in the other groups, P ≤ .04) and had lower asthma control after 1 year of optimal management (P ≤ .006). ASM enlargement occurred independently of features of airway inflammation and remodeling, whereas it was associated with PAR-2 overexpression and higher alveolar tryptase (P ≤ .02) and KLK14 (P ≤ .03) levels. CONCLUSION: Increase in ASM mass, possibly involving aberrant expression and activation of PAR-2-mediated pathways, characterizes younger patients with severe asthma with poor asthma control.


Asunto(s)
Asma/metabolismo , Músculo Liso/patología , Receptor PAR-2/metabolismo , Adulto , Anciano , Remodelación de las Vías Aéreas (Respiratorias) , Asma/inmunología , Asma/patología , Asma/fisiopatología , Bronquios/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Humanos , Calicreínas/metabolismo , Ligandos , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Triptasas/metabolismo , Capacidad Vital
17.
Eur Respir J ; 48(6): 1721-1731, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27836952

RESUMEN

Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival.237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046).TERT/TERC DAV were associated with specific clinical and biological features and reduced transplant-free survival.


Asunto(s)
Fibrosis Pulmonar Idiopática/genética , ARN/genética , Telomerasa/genética , Telómero/genética , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Francia/epidemiología , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
18.
COPD ; 12 Suppl 1: 46-51, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25938292

RESUMEN

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.


Asunto(s)
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/psicología
19.
Eur Respir J ; 44(1): 78-86, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24525449

RESUMEN

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.


Asunto(s)
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/mortalidad
20.
Am J Respir Crit Care Med ; 187(12): 1335-40, 2013 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23590274

RESUMEN

RATIONALE: The survival benefit of lung transplantation (LT) in adult patients with cystic fibrosis (CF) is debated. OBJECTIVES: We sought to assess the survival benefit of LT in adult patients with CF. METHODS: We used data from the United Network for Organ Sharing Registry to identify adult patients with CF on a wait list for LT in the United States between 2005 and 2009. Survival times while on the wait list and after LT were modeled by use of a Cox model that incorporated transplantation status as a time-dependent covariate. Evolution in lung allocation score (LAS) while on the wait list was used as a surrogate for disease severity. We fitted a model for the joint distribution of survival and longitudinal disease process (LAS over time). MEASUREMENTS AND MAIN RESULTS: A total of 704 adult patients with CF were registered on a wait list during the study period. The cumulative incidence of LT was 39.3% (95% confidence interval, 35.6-42.9%) at 3 months and 64.7% (61.0-68.4%) at 12 months, whereas the incidence of death while on the wait list at the same times was 8.5% (6.4-10.6%) and 12.9% (10.3-15.5%), respectively. Survival after LT was 96.5% (94.7-98.2%) at 3 months; 88.4% (85.1-91.8%) at 12 months; and 67.8% (59.9-76.8%) at 3 years. LT conferred a 69% reduction in the instantaneous risk of death (51-80%). The interaction between LAS and LT was significant: the higher the LAS, the greater the survival benefit of LT (P < 0.001). CONCLUSIONS: LT confers a survival benefit for adult patients with CF.


Asunto(s)
Fibrosis Quística/mortalidad , Fibrosis Quística/cirugía , Trasplante de Pulmón , Adolescente , Adulto , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Obtención de Tejidos y Órganos/estadística & datos numéricos , Listas de Espera , Adulto Joven
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