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1.
Eur Respir Rev ; 29(156)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32620589
4.
Eur Respir J ; 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527740

RESUMO

Tyrosine kinase inhibitors (TKIs) targeting the Bcr-Abl oncoprotein revolutionised the treatment of chronic myelogenous leukemia. Following the success of imatinib, second and third generation molecules were developed. Different profiles of kinase inhibition and off-target effects vary between TKIs, which leads to a broad spectrum of potential toxicities.Pulmonary complications are most frequently observed with dasatinib but all other Bcr-Abl TKIs have been implicated. Pleural effusions are the most frequent pulmonary complication of TKIs, usually associated with dasatinib and bosutinib. Pulmonary arterial hypertension is an uncommon but serious complication of dasatinib, which is often reversible upon discontinuation. Bosutinib and ponatinib have also been associated with pulmonary arterial hypertension, while imatinib has not. Rarely, interstitial lung disease has been associated with TKIs, predominantly with imatinib.Mechanistically, dasatinib affects maintenance of normal pulmonary endothelial integrity by generating mitochondrial oxidative stress, inducing endothelial apoptosis and impairing vascular permeability in a dose-dependent manner. The mechanisms underlying other TKI-related complications are largely unknown. Awareness and early diagnosis of the pulmonary complications of Bcr-Abl TKIs is essential given their seriousness, potential reversibility, and impact on future treatment options for the underlying chronic myelogenous leukemia.

6.
Presse Med ; 49(2): 104022, 2020 May 07.
Artigo em Francês | MEDLINE | ID: mdl-32387530
8.
Artigo em Inglês | MEDLINE | ID: mdl-32437637

RESUMO

RATIONALE: Pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1) is a rare and largely unknown complication of NF1. OBJECTIVES: To describe characteristics and outcomes of PH-NF1. METHODS: We reported the clinical, functional, radiologic, histologic and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs and transplant-free survival of patients with PH-NF1 from the French PH registry. RESULTS: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median age at diagnosis of 62 [18-82] years. At diagnosis, 92% were in New York Heart Association (NYHA) functional class III or IV. The 6-minute walk distance was 211 [0-460] m. Pulmonary function tests showed low diffusing capacity of the lung for carbon monoxide (DLCO) (30 [12-79] %) and severe hypoxemia (PaO2 56 [38-99] mmHg). Right heart catheterization showed severe precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure of 45 (10) mmHg and a pulmonary vascular resistance of 10.7 (4.2) WU. High-resolution computed tomography revealed cysts (76%), ground glass opacities (73%), emphysema (49%) and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3 and 5 years was 87%, 54% and 42%, respectively, and 4 patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling. CONCLUSIONS: PH-NF1 is characterized by a female predominance, a low DLCO and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

9.
Eur Respir Rev ; 29(156)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32461209

RESUMO

Pulmonary capillary haemangiomatosis (PCH) is a rare and incompletely understood histopathological finding characterised by abnormal capillary proliferation within the alveolar interstitium, which has long been noted to share many overlapping features with pulmonary veno-occlusive disease (PVOD). But are PCH and PVOD distinct entities that occur in isolation, or are they closely intertwined manifestations along a spectrum of the same disease? The classic clinical features of both PCH and PVOD include signs and symptoms related to pulmonary hypertension, hypoxaemia, markedly impaired diffusion capacity of the lung and abnormal chest imaging with ground glass opacities, septal lines and lymphadenopathy. In recent years, increasing evidence suggests that the clinical presentation, histopathological features, genetic substrate and pathobiological mechanisms of PCH and PVOD are overlapping and usually indistinguishable. The discovery of biallelic mutations in the eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) gene in heritable PCH and PVOD greatly advanced our understanding of the overlapping nature of these conditions. Furthermore, recognition of PCH and PVOD-like changes in other pulmonary vascular diseases and in conditions that cause chronic pulmonary venous hyper-perfusion or hypertension suggests that PCH/PVOD may develop as a reactive process to various insults or injuries to the pulmonary vasculature, rather than being primary angiogenic disorders.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32352834

RESUMO

RATIONALE: Idiopathic and hereditary pulmonary arterial hypertension (PAH) are rare but comprise a genetically heterogeneous patient group. RNA-sequencing linked to the underlying genetic architecture can be used to better understand the underlying pathology by identifying key signalling pathways and stratify patients more robustly according to clinical risk. OBJECTIVES: Using a three-stage design of RNA discovery, RNA validation/model construction and model validation to define a set of PAH-associated RNAs and a single summarising RNA model score. To define genes most likely to be involved in disease development, we performed Mendelian randomisation (MR) analysis. METHODS: RNA-sequencing was performed on whole blood samples from 359 patients with idiopathic, heritable and drug-induced PAH and 72 age- and sex-matched healthy volunteers. The score was evaluated against disease severity markers including survival analysis using all-cause mortality from diagnosis. MR used known eQTL and summary statistics from a PAH GWAS. MEASUREMENTS AND MAIN RESULTS: We identified 507 genes with differential RNA expression in PAH patients compared to controls. A model of 25 RNAs was able to distinguish PAH with 87% accuracy (AUC 95% CI: 0.791-0.945) in model validation. The RNA model score was associated with disease severity and long-term survival (p=4.66x10-6) in PAH. MR detected an association between SMAD5 levels and PAH disease susceptibility (OR:0.317, 95%CI:0.129-0.776, p=0.012). CONCLUSIONS: A whole blood RNA signature of PAH, which includes RNAs relevant to disease pathogenesis, associates with disease severity and identifies patients with poor clinical outcomes. Genetic variants associated with lower SMAD5 expression may increase susceptibility to PAH. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

12.
Eur Respir J ; 55(6)2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32241829

RESUMO

BACKGROUND: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU. METHODS: This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated. FINDINGS: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL-1 at baseline to 92 cells·µL-1 at 24 months of follow-up; lung function and asthma control followed a similar trend. INTERPRETATION: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial.

13.
Rev Med Suisse ; 16(N° 691-2): 835-838, 2020 Apr 29.
Artigo em Francês | MEDLINE | ID: mdl-32348047

RESUMO

Most patients hospitalized for COVID-19 are aged over 70 years old, and half of those who die are over 83 years old. Older patients do not always present with typical symptoms (fever, cough and dyspnoea) but sometimes are and remain asymptomatic (contact screening), or have aspecific presentations (altered general condition, falls, delirium, unusual fatigue). Rectal swab, which minimizes exposition risk, appears useful in long-term care patients with diarrhea. Older age is associated with worse prognosis, but the analysis should be refined by means of prognostic indexes that account for the heterogeneous health, functional, and cognitive status of the elderly population. Gathering elderly patients' wishes and assessing their remaining life expectancy allows to anticipate care decisions according to the level of tension in the health system.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Humanos , Expectativa de Vida , Preferência do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Prognóstico , Suíça
14.
J Asthma ; : 1-6, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32347748

RESUMO

Since their introduction many decades ago, systemic corticosteroids have become a mainstay treatment for asthma. Despite being a highly effective therapy, corticosteroids can cause significant adverse effects in patients. This results in a "double hit" for some patients as they suffer the burden of disease as well as the burden of treatment-induced morbidity.This article aims to raise awareness of the potential, harmful side effects of prolonged or repeated exposure to systemic corticosteroids in asthma. It also highlights the importance of referral of the appropriate patients with asthma from primary care for specialist assessment once other considerations such as adherence, inhaler technique and co-morbidity have been evaluated. We propose a simple decision step that may help busy primary care physicians and general practitioners to identify patients who could benefit from specialist assessment.Our decision step suggests that a patient with asthma should be reviewed at least once by an asthma specialist if he/she (i) has received ≥2 courses of oral corticosteroids in the previous year; asthma remains uncontrolled despite good adherence and inhaler technique; or (ii) has attended an emergency department or was hospitalized for asthma care.Such referral could facilitate wider access to diagnostic tools, in-depth assessment of confounding comorbidities, and non-corticosteroid-based therapies as needed, which may be unavailable in primary practice.

16.
Chest ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32275978

RESUMO

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.

17.
Radiology ; 296(1): 172-180, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255413

RESUMO

With more than 900 000 confirmed cases worldwide and nearly 50 000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Radiografia Torácica/métodos , Consenso , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Saúde Global , Fidelidade a Diretrizes , Humanos , Equipamento de Proteção Individual , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Radiografia Torácica/instrumentação , Índice de Gravidade de Doença , Sociedades Médicas , Triagem , Gravação em Vídeo
18.
ESC Heart Fail ; 7(2): 747-756, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32147955

RESUMO

AIMS: In univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. We present the SV-INHIBITION study rationale, design, and methods. METHODS AND RESULTS: The SV-INHIBITION trial is a nationwide multicentre, randomized, double blind, placebo-controlled, Phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in teenagers and adult patients (>15 years old) with an SV. Patients with a mean pulmonary arterial pressure >15 mmHg and a trans-pulmonary gradient >5 mmHg, measured by cardiac catheterization, will be eligible. The primary outcome is the variation of the VE/VCO2 slope, measured by a cardiopulmonary exercise test, between baseline and 6 months of treatment. A total of 50 patients are required to observe a decrease of 5 ± 5 points in the VE/VCO2 slope, with a power of 90% and an alpha risk of 5%. The secondary outcomes are clinical outcomes, oxygen saturation, 6 min walk test, SV function, NT-proBNP, peak VO2 , stroke volume, mean pulmonary arterial pressure, trans-pulmonary gradient, SF36 quality of life score, safety, and acceptability. CONCLUSIONS: The SV-INHIBITION study aims to answer the question whether PDE5 inhibitors should be prescribed in patients with an SV. This trial has been built focusing on the three levels of research defined by the World Health Organization: disability (exercise tolerance), deficit (SV function), and handicap (quality of life).

19.
Eur Respir J ; 55(6)2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32184319

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). Untreated CTEPH is fatal, but, if diagnosed in time, successful surgical (pulmonary endarterectomy), medical (pulmonary hypertension drugs) and/or interventional (balloon pulmonary angioplasty) therapies have been shown to improve clinical outcomes, especially in case of successful pulmonary endarterectomy. Early diagnosis has however been demonstrated to be challenging. Poor awareness of the disease by patients and physicians, high prevalence of the post-PE syndrome (i.e. persistent dyspnoea, functional limitations and/or decreased quality of life following an acute PE diagnosis), lack of clear guideline recommendations as well as inefficient application of diagnostic tests in clinical practice lead to a reported staggering diagnostic delay >1 year. Hence, there is a great need to improve current clinical practice and diagnose CTEPH earlier. In this review, we will focus on the clinical presentation of and risk factors for CTEPH, and provide best practices for PE follow-up programmes from expert centres, based on a clinical case.

20.
Arch Bronconeumol ; 2020 Feb 25.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32111418

RESUMO

BACKGROUND AND OBJECTIVE: Ventilatory inefficiency (high V'E/V'CO2) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO2 suggests increased chemosensitivity or an altered PaCO2 set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO2 set-point, exercise capacity, hemodynamics and V'E/V'CO2. METHODS: Pulmonary arterial hypertension (n=34), chronic thromboembolic pulmonary hypertension (CTEPH, n=19) and pulmonary veno-occlusive disease (PVOD, n=6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO2: hypocapnic (PaCO2 ≤34mmHg) or normocapnic (PaCO2 35-45mmHg). The PaCO2 set-point was estimated by the maximal value of end-tidal PCO2 (maximal PETCO2) between the anaerobic threshold and respiratory compensation point. RESULTS: The hypocapnic group (n=39) had lower resting cardiac index (3.1±0.8 vs. 3.7±0.7L/min/m2, p<0.01), lower peak V'O2 (15.8±3.5 vs. 20.7±4.3mL/kg/min, p<0.01), and higher V'E/V'CO2 slope (60.6±17.6 vs. 38.2±8.0, p<0.01). At peak exercise, hypocapic patients had lower PaO2, higher VD/VT and higher P(a-ET)CO2. Maximal PETCO2 (r=0.59) and VD/VT (r=-0.59) were more related to cardiac index than PaO2 or PaCO2 at rest or peak exercise. Maximal PETCO2 was the strongest correlate of V'E/V'CO2 slope (r=-0.86), peak V'O2 (r=0.64) and peak work rate (r=0.49). CONCLUSIONS: Resting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO2 set-point. Maximal PETCO2 may be a useful non-invasive marker of PaCO2 setpoint and disease severity even with submaximal effort.

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