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Evaluation of inflammation of the airways in asthma: development of experimental models and clinical studies


Asthma is the most common chronic disease of childhood and is also very common in adults. Between 3 and 10% of the world population have asthma. Some studies suggest that, at least in some countries, the incidence, severity and mortality of asthma are increasing. Asthma is a disease with a high economic impact and also affects quality of life. It is now well established that asthma is a chronic inflammatory disease, and one definition of asthma is from the Global Initiative for Asthma, a meeting sponsored by the World Health Organization in 1995: "asthma is a chronic inflammatory syndrome of airways, where various cells play a key hole, such as eosinophils, mast cells and T lymphocytes. In suscetible people, this inflammation results in a variety of symptoms such as wheezing, cough and shortness of breath, specially at night and early morning. This symptoms are associated with airway obstruction that is, at least partially, reversible either spontaneously or with treatment. This inflammation is associated to airway hyperresponsiveness to a -variety of stimuli". The observation of the critical hole of inflammation in asthma resulted in many studies designed to better understand the pathophysiology of airway inflammation, the relationship between airway inflammation and airway hyperresponsiveness, the development of methods to evaluate the severity of inflammation of patients with asthma and programs of asthma treatment based in the use of anti-inflammatory drugs, specially corticosteroids. The main purpose of our studies is to consolidate a multidisciplinar research group of the Faculty of Medicine of the University of São Paulo, that has been studying asthma as antinflammatory disease, performing laboratory and clinical studies with children and adults with asthma. During the three years of our studies we will perform the following experimental protocols: a) the study of new methods to evaluate asthma severity, specially sputum cytology and measurements of exaled nitric oxide levels, both in children and adults with asthma; b) the study of mechanisms of dyspnea in exercise-induced asthma and the relationship between exercise response and asthma severity; c) the study of the relationship between asthma and rhinitis and sinusitis, specifically the effects of the treatment of rhinitis and sinusitis on asthma; d) the comparison of airway responsiveness to bradykinin and methacholine in some subgroups of asthmatic people: exercise-induced asthma, asthma associated to gastroesophageal reflux and nocturnal asthma; e) the study of lungs of patients who died of asthma, specifically the hole of extracellular matrix in airway obstruction; f) the development of experimental models to study the pathophysiology of asthma associated to gastroesophageal reflux; g) the development of experimental models of hyperventilation to study the mechanisms of exercise-induced asthma6; h) the study of the hole of capsaicin-sensitive sensory nerves on the pathophysiology of chronic airway inflammation induced by allergen; i) the development of methods to evaluate pulmonary responsiveness to bronchoconstrictive agonists in mice and the study of pulmonary hyperresponsiveness in mice submitted to protocols of sensitization with allergens using different adjuvants; j) the study of the effects of chronic treatment with beta-2 agonists on sensitization and inflammation of airways induced by ovalbumin. (AU)

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