Asunto(s)
Pérdida de Sangre Quirúrgica , Mesotelioma , Atención Perioperativa/métodos , Derrame Pleural/diagnóstico , Neoplasias Pleurales , Tórax/diagnóstico por imagen , Anciano , Amianto/efectos adversos , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Masculino , Mesotelioma/complicaciones , Mesotelioma/etiología , Mesotelioma/patología , Exposición Profesional/efectos adversos , Derrame Pleural/etiología , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/etiología , Neoplasias Pleurales/patología , Toracoscopía/efectos adversos , Toracoscopía/métodos , Resultado del Tratamiento , UltrasonografíaRESUMEN
INTRODUCTION: Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. METHODS AND ANALYSIS: Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12â h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. IMPLICATIONS: Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. ETHICS AND DISSEMINATION: This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proyectos de Investigación , Fumar/inmunología , Fumar/metabolismo , Administración por Inhalación , Humanos , Modelos Biológicos , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Enfisema Pulmonar/inmunología , Enfisema Pulmonar/metabolismoRESUMEN
Clinical trials with new drugs for chronic obstructive pulmonary disease (COPD) have been performed. Viruses exacerbate COPD and bacteria may play a part in severe COPD; therefore, antibiotic and antiviral approaches have a sound rationale. Antiinflammatory approaches have been studied. Advances in understanding the molecular basis of other processes have resulted in novel drugs to target reactive oxidant species, mucus, proteases, fibrosis, cachexia, and muscle wasting, and accelerated aging. Studies with monoclonal antibodies have been disappointing, highlighting the tendency for infections and malignancies during treatment. Promising future directions are lung regeneration with retinoids and stem cells.
Asunto(s)
Corticoesteroides/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Dispositivos para Dejar de Fumar Tabaco , Administración por Inhalación , Quimioterapia Combinada , Humanos , Cese del Hábito de Fumar/métodosRESUMEN
HIV is an increasingly common cause of thrombotic thrombocytopaenic purpura in the United Kingdom. We report a patient with both conditions who presented major therapeutic and ethical challenges. Furthermore, he was recalcitrant to all established therapies, and was, therefore, the first reported HIV patient with thrombotic thrombocytopaenic purpura to receive rituximab.