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BACKGROUND: Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. METHODS: A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. RESULTS: Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. CONCLUSION: Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.
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Analgésicos Opioides/uso terapêutico , Dispneia/tratamento farmacológico , Dispneia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Doença Crônica , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Prevalência , Estudos Prospectivos , Pneumologistas , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients.
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Asma/complicações , Asma/diagnóstico , Fenótipo , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso , Asma/tratamento farmacológico , Asma/epidemiologia , Estudos de Coortes , Comorbidade , Diagnóstico Diferencial , Progressão da Doença , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários , Avaliação de Sintomas , SíndromeRESUMO
INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.
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Asma , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Humanos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Asma/complicações , Asma/diagnóstico , Asma/tratamento farmacológicoRESUMO
INTRODUCTION: The first COPD biennial organized by the French Society of Respiratory Diseases (SPLF) took place on 17 December 2021. STATE OF THE ART: The objective of the biennial was to discuss current knowledge regarding COPD pathophysiology, current treatments, research development, and future therapeutic approaches. PERSPECTIVES: The different lecturers laid emphasis on the complexity of pathophysiologic mechanisms including bronchial, bronchiolar and parenchymal alterations, and also dwelt on the role of microbiota composition in COPD pathenogenesis. They pointed out that addition to inhaled treatments, ventilatory support and endoscopic approaches have been increasingly optimized. The development of new therapeutic pathways such as biotherapy and cell therapy (stem cells ) call for further exploration. CONCLUSIONS: The dynamism of COPD research was repeatedly underlined, and needs to be further reinforced, the objective being to "understand so as to better innovate" so as to develop effective new strategies for treatment and management of COPD.
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Microbiota , Doença Pulmonar Obstrutiva Crônica , Transtornos Respiratórios , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.
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Transplante de Pulmão , Insuficiência Respiratória , Humanos , Qualidade de Vida , Transplante de Pulmão/métodos , França/epidemiologia , Contraindicações , Insuficiência Respiratória/etiologiaRESUMO
Pseudomonas aeruginosa (PA) airway infection and bronchial blood vessel proliferation are features of bronchiectasis. Because vascular endothelial growth factor (VEGF)-A regulates angiogenesis, we hypothesised that PA infection induces VEGF synthesis in epithelium and peribronchial angiogenesis. Because epidermal growth factor receptor (EGFR) activation regulates VEGF synthesis in cancer, we also evaluated the roles of EGFR. Airway epithelial cells were incubated for 24 h with PA supernatants and VEGF concentrations were measured in culture medium by ELISA. C57BL/6N mice were instilled intratracheally with sterile agarose beads or with agarose beads coated with the PA strain PAO1 (mean ± sem 6 × 10(5) ± 3 × 10(5) cfu · animal(-1)), with or without the EGFR inhibitor AG1478 (12.5 mg · kg(-1) · day(-1) intraperitoneally). Epithelial immunostaining for VEGF and phosphorylated EGFR, and peribronchial vascularity, were quantified using morphometric analysis. VEGF expression was further assessed by western blot in mouse lung homogenates. PA supernatants induced dose-dependent VEGF synthesis in cultured airway epithelial cells, effects which were prevented by EGFR antagonists. In mice, persistent PAO1 infection increased immunostaining for VEGF and phosphorylated EGFR in airway epithelium, and resulted in increased peribronchial vascularity within 7 days. These effects were reduced by EGFR inhibition. Persistent PA infection induced VEGF synthesis in airway epithelium and peribronchial angiogenesis, at least in part via EGFR-dependent mechanisms.
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Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/metabolismo , Mucosa Respiratória/metabolismo , Mucosa Respiratória/microbiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Bronquiectasia/metabolismo , Bronquiectasia/microbiologia , Carcinoma Mucoepidermoide , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/metabolismo , Feminino , Humanos , Técnicas In Vitro , Neoplasias Pulmonares , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Neovascularização Patológica/microbiologia , Circulação Pulmonar/fisiologia , Mucosa Respiratória/irrigação sanguínea , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
INTRODUCTION: Fungal aspergillosis colonization and allergic bronchopulmonary aspergillosis (ABPA) can have a strong impact on the prognosis in cystic fibrosis (CF). We conducted round table discussions involving French experts from pediatric and adult centers caring for patients with CF, microbiologists, radiologists and pharmacists. The aim was to explore the current state of knowledge on: the pathophysiological mechanisms of Aspergillus and other micromycetes infections in CF (such as Scedosporium sp.), and on the clinico-biological diagnosis of ABPA. In perspective, the experts explored the role of imaging in the diagnosis of APBA, specifically CT and MRI; as well as the role of bronchoscopy in the management. We also reviewed the therapeutic management, including different corticosteroid regimens, antifungals and anti-IgE antibodies. CONCLUSION: The diagnosis of ABPA in CF should be based on more standardized biological assays and imaging to optimize treatment and follow-up.
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Aspergilose Broncopulmonar Alérgica , Fibrose Cística , Corticosteroides , Adulto , Antifúngicos/uso terapêutico , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergillus fumigatus , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , HumanosRESUMO
BACKGOUND: Elexacaftor-tezacaftor-ivacaftor partially restores cystic fibrosis transmembrane conductance regulator function, and has been shown to induce significant clinical improvement in patients with at least one Phe508del allele. Yet little data exist on patient perspectives following elexacaftor-tezacaftor-ivacaftor initiation. METHODS: A mixed methods study was conducted using an online 13-item questionnaire (including 9 closed questions and 4 open questions), submitted from July 10th to August 21th 2020 to French patients aged 12 years and older with advanced CF who were treated with elexacaftor-tezacaftor-ivacaftor. Their responses were summarized as numbers (%), and free-text items were analysed using a grounded theory approach. RESULTS: Of 245 patients who started elexacaftor-tezacaftor-ivacaftor in France, 101 (41%) participated. Median [IQR] age was 35 [28-41] years and duration of elexacaftor-tezacaftor-ivacaftor treatment was 4.3 [3.0-5.6] months. Patients generally reported a rapid impact on respiratory symptoms, sleep quality, general well-being and physical self-esteem, and a reduction in overall treatment burden. The majority of patients contrasted treatment burden, symptom severity, depression and a closed future marked by death or transplantation before elexacaftor-tezacaftor-ivacaftor, to renewed and unexpected physical strength, leading to greater self-confidence, autonomy and long-term planning, after treatment initiation. A small number of patients expressed concerns, mainly regarding changes in body representation and/or the fear of becoming dependent on the treatment. CONCLUSION: After initiation of elexacaftor-tezacaftor-ivacaftor, CF patients with advanced disease reported rapid and positive physical, psychological and social effects, which translated into improved quality of life and the formulation of new life goals.
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Fibrose Cística , Adulto , Aminofenóis , Benzodioxóis , Agonistas dos Canais de Cloreto , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Humanos , Indóis , Mutação , Pirazóis , Piridinas , Pirrolidinas , Qualidade de Vida , Quinolonas , Qualidade do SonoRESUMO
Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.
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Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Análise por Conglomerados , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Análise de Componente Principal , Doença Pulmonar Obstrutiva Crônica/classificação , Pneumologia/métodos , Projetos de PesquisaRESUMO
Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene CFTR. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways. We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages. In lungs from Cftr(-/-) mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression. Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.
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Brônquios/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fosfolipases A2 do Grupo IV/genética , Fosfolipases A2 do Grupo IV/metabolismo , Mucina-5AC/metabolismo , Muco/metabolismo , Animais , Ácido Araquidônico/metabolismo , Brônquios/citologia , Linhagem Celular , Cloretos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Citosol/metabolismo , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CFTR , Mucina-5AC/genética , RNA Interferente Pequeno , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismoRESUMO
BACKGROUND: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation. METHODS: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). RESULTS: Forty-two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease (n = 25), congenital absence of the vas deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24-41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39-63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV(1)) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation. CONCLUSIONS: When present in trans with a CF-causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival.
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Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Predisposição Genética para Doença , Mutação/genética , Adolescente , Adulto , Idoso , Substituição de Aminoácidos/genética , Criança , Pré-Escolar , Cloretos/análise , Estudos de Coortes , Consenso , Fibrose Cística/classificação , Fibrose Cística/diagnóstico , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado/genética , Homozigoto , Humanos , Masculino , Potenciais da Membrana/fisiologia , Pessoa de Meia-Idade , Mucosa Nasal/fisiopatologia , Suor/química , Adulto JovemRESUMO
Cystic fibrosis (CF) is a channelopathy caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Diagnosis of CF has long relied on a combination of clinical (including gastrointestinal and/or respiratory) symptoms and elevated sweat chloride concentration. After cloning of the CFTR gene in 1989, genetic analysis progressively became an important aspect of diagnosis. Although combination of sweat test and genetic analysis have simplified the diagnosis of CF in most cases, difficult situations remain, especially in cases that do not fulfill all diagnostic criteria. Such situations are most frequently encountered in patients presenting with a single-organ disease (e.g., congenital absence of the vas deferens, pancreatitis, bronchiectasis) leading to a diagnosis of CFTR-related disorder, or when the presence/ absence of CF is not resolved after newborn screening. This article reviews the diagnostic criteria of CF, with special emphasis on genetic testing. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
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Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Mutação , Algoritmos , Bronquiectasia/genética , Fibrose Cística/genética , Insuficiência Pancreática Exócrina/genética , Testes Genéticos , Humanos , Recém-Nascido , Ceratodermia Palmar e Plantar/genética , Masculino , Triagem Neonatal , Pancreatite Crônica/genética , Rinite/genética , Sinusite/genética , Suor/química , Ducto Deferente/anormalidadesRESUMO
INTRODUCTION: The relations between chronic obstructive pulmonary disease (COPD) and respiratory diseases due to Aspergillus spp. are not well understood. METHODS: We analysed a retrospective series of patients hospitalized with a diagnosis of COPD and respiratory disease due to Aspergillus. Patients were identified between 2010 and 2015 from the medico-administrative database of Cochin hospital, Paris. Historical, clinical, biological, microbiological and imaging data were collected and described. Diagnoses were reclassified based on reference definitions and classifications from the literature. Patients were classified according to the type of Aspergillus-related diseases and risk factors were described. RESULTS: Forty patients were identified. Classifiable Aspergillus-related respiratory conditions were confirmed in 26 of them including 12 allergic bronchopulmonary aspergillosis (ABPA), 8 chronic pulmonary aspergillosis (CPA), 1 invasive pulmonary aspergillosis (IPA) and 3 diagnostic associations ABPA/CPA. Other respiratory comorbidities were present in all cases of CPA and immunodepression was recorded for semi-invasive and invasive forms. Finally, 16 patients could not be classified, among whom Aspergillus related lung disease was considered as likely in one-half. CONCLUSION: The complexity of the diagnosis of pulmonary aspergillosis is related to its multiple types with sometimes unclear distinctions. Any type of pulmonary aspergillosis can be observed in patients with COPD, depending on associated risks factors. It would be helpful to establish specific classifications adapted to patients with COPD. This will require larger, prospective, multicentre studies.
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Aspergilose Pulmonar/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/epidemiologia , Aspergilose Broncopulmonar Alérgica/microbiologia , Comorbidade , Diagnóstico Diferencial , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doenças Respiratórias/complicações , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/microbiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1. METHODS: Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated. RESULTS: In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts. CONCLUSION: After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.
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Diferenciação Celular , Mucosa Nasal/citologia , Cicatrização , Dineínas do Axonema , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cílios/metabolismo , Regulação para Baixo , Dineínas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Queratina-14/metabolismo , Mucina-5AC/genética , Mucina-5AC/metabolismo , Mucinas/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Tubulina (Proteína)/metabolismoRESUMO
Two strategies are possible for targeting distal airways in asthma. The first one is systemic, with the delivery of medications either orally or intravenously. Montelukast is the only oral drug that has demonstrated its efficacy on distal airways by reducing lung hyperinflation. The second possible strategy is to deliver inhaled medications using ultrafine particles. Studies performed with formoterol-HFA solution (Formoair Modulite), the only available long-acting beta2 agonist with ultrafine particles have shown a non-inferior bronchodilator effect and a good tolerance as compared to inhaled long acting beta2 agonists with non-ultrafine particles. Studies performed with BDP-HFA alone (QVAR) or combined BDP-HFA/formoterol (Fostair) with ultrafine particles have mostly demonstrated their clinical non- inferiority on bronchodilation, quality of life, and symptoms in asthmatic subjects as compared to non-ultrafine inhaled medications. With the exception of a few studies, most publications have been performed in a limited number of patients and for only short durations. The available studies have not yet demonstrated a long-term benefit in terms of additional clinical efficacy of these ultrafine inhaled medications on symptoms, control and exacerbations of asthma.
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Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Etanolaminas/uso terapêutico , Fumarato de Formoterol , Humanos , Nebulizadores e Vaporizadores , Tamanho da PartículaRESUMO
INTRODUCTION: Cystic fibrosis is usually diagnosed during the first years of life. Diagnosis may be achieved in adults with milder forms of the disease at any age. CASE REPORTS: We report the diagnosis of cystic fibrosis in three adults within the same family. A 39 yr old man, was diagnosed with congenital absence of the vas deferens; the diagnosis of cystic fibrosis was achieved based on a positive chloride sweat test and the identification of two mutations in the CFTR gene. His mother experienced repeated bronchial infections that began when she was 12 years old. The diagnosis of cystic fibrosis was considered at the age of 74 yr after her son was diagnosed with this disease. Sweat test showed normal chloride concentrations and cystic fibrosis was suspected based on elevated basal transepithelial nasal potential difference. Genetic testing for the 33 most frequent mutations in the CFTR gene showed only one mutation. A second rare mutation was identified by complete sequencing of the CFTR gene, confirming the diagnosis of cystic fibrosis. A third case of pauci-symptomatic cystic fibrosis was diagnosed in a brother of the index case. CONCLUSION: These observations illustrate the challenge of diagnosing milder forms of cystic fibrosis in adult subjects. The recognition of this diagnosis may lead to improvement in patient's care and to genetic counselling.
Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/genética , Adulto , Fatores Etários , Idoso , Bronquiectasia/diagnóstico por imagem , Criança , Cloretos/análise , Fibrose Cística/diagnóstico por imagem , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Radiografia Torácica , Suor/química , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT. MATERIALS AND METHODS: A total of 52 patients with CF who underwent LT at our institution between January 2001 and December 2006 with at least 3 years of survival were retrospectively included. There were 27 men and 25 women with a mean age of 24.4±9.2 (SD) years (range: 7.6-52.9 years) at the time of LT. Calculation of cumulative effective and organ doses after LT were based on dosimetry information and acquisition parameters of each examination. Cumulative radiation doses were calculated until June 2016, but stopped at the time of de novomalignancy diagnosis, for patients developing the condition. RESULTS: Patients received a mean cumulative effective dose of 110.0±51.6 (SD) mSv (range: 13-261.3 mSv) over a mean follow-up of 8.1±3.6 (SD) years (range: 0.5-13.5 years), with more than 100mSv in 5 years in 19/52 patients (37%). Chest CT accounted for 73% of the cumulative effective dose. Mean doses to the lung, breast and thyroid were 152.8±61.1 (SD) mGy (range: 21.2-331.6 mGy), 106.5±43.2 (SD) mGy (range: 11.9-221.4 mGy) and 72.7±31.8 (SD) mGy (range: 9.5-165.0 mGy), respectively. Nine out of 52 patients (17%) developed a total of 10 de novo malignancies, all but one attributable to immunosuppression after a mean post-transplantation follow-up period of 11.1±3.5 (SD) years (range: 3.7-16.3 years). Six-month cumulative effective dose was not greater in patients with de novomalignancies than in those without de novomalignancies (28.9±14.5 (SD) mGy (range: 13.0-53.4) vs 25.6±15.3 (range: 5.0-69.7), respectively, P>0.05). CONCLUSION: The cumulative effective dose exceeded 100 mSv in 5 years in 37% of LT recipients, the reason why continuous efforts should be made to optimize chest CT acquisitions accounting for 73% of the radiation dose.
Assuntos
Fibrose Cística/diagnóstico por imagem , Fibrose Cística/cirurgia , Transplante de Pulmão , Órgãos em Risco/efeitos da radiação , Doses de Radiação , Lesões por Radiação/etiologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Criança , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Radiometria , Adulto JovemRESUMO
Inhaled air is contaminated with pathogens and particulates that may deposit in the airways and damage the host. In response to these invaders, the airway epithelium has developed innate immune responses that provide a defence against the invaders and protect the airway structure and function. Thus, the epithelium of conducting airways becomes the "battleground" between the invaders and the host. Recent evidence suggests that airway epithelial surface signalling through the epidermal growth factor receptor (EGFR) is a convergent pathway producing innate immune responses to a variety of infectious and noninfectious noxious stimuli. In the present review, the EGFR signalling pathways leading to airway mucin production, neutrophil recruitment (via interleukin-8 production) and airway epithelial repair were examined. The importance of these findings in human airway diseases was also investigated. The current authors suggest that the exaggerated innate immune responses found in chronic inflammatory airway diseases (e.g. chronic obstructive pulmonary disease, cystic fibrosis and severe asthma) contribute to the pathogenesis or the aggravation of these diseases. Potential therapies include inhibition of the various elements of the described epidermal growth factor receptor cascade. In considering each therapeutic intervention, the potential benefits must be considered in relation to potential deleterious effects.
Assuntos
Asma/metabolismo , Fibrose Cística/metabolismo , Receptores ErbB/metabolismo , Imunidade Inata , Mucinas/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Asma/diagnóstico , Fibrose Cística/diagnóstico , Humanos , Interleucina-8/metabolismo , Ligantes , Modelos Biológicos , Neutrófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Espécies Reativas de Oxigênio , Transdução de SinaisRESUMO
Eosinophilic pleural effusion (EPE) is defined as pleural eosinophilia greater than 10%. EPE can be seen in almost all conditions that can cause pleural effusion, but some aetiologies have to be investigated due to their frequency or potential severity. The most common aetiology of EPE is the presence of air or blood in the pleural cavity. Other frequent aetiologies include bacterial pneumonia, tuberculosis, parasitic disease and certain drugs. Although often considered to be a sign of a benign condition, pleural eosinophilia may be associated with malignancies. EPE may also indicate the presence of Churg and Strauss syndrome. We report the case of a 27-year-old man, in whom the exploration of EPE led to the diagnosis of Churg and Strauss syndrome with the association of asthma, blood and alveolar eosinophilia, myopericarditis and positive antineutrophil cytoplasmic antibodies (ANCA). This case report enables us to discuss the different causes of EPE and to illustrate how it may be a manifestation of Churg and Strauss syndrome.