Mechanisms of pulmonary inflammation in asthma: clinical and experimental studies

Abstract

Asthma is the most common chronic disease in children and has also a high prevalence among all ages. The prevalence of asthma is increasing and asthma is a very important health issue. Brazil is a country with high prevalence of asthma. Asthma is a clinical syndrome with a substantial economic impact and affects significantly the quality of life although has a low mortality. It is well established that asthma corresponds a specific type of chronic inflammation of airways, although the precise etiology of this inflammation is not well understood. Multiple aspects of the inflammatory syndrome in asthma deserve more studies, including the precise role of each inflammatory cell type and the best way to evaluate the severity of airway inflammation and the response to treatment. The understanding of asthma as a chronic inflammatory syndrome influenced the development of multiple experimental and clinical studies concerning the pathophysiology of airway inflammation, the relationship between pulmonary inflammation and bronchial hyperresponsiveness, the best strategies to evaluate the severity and the treatment of airway inflammation and the development of programs of long term care of asthmatics. The main purpose of this project is to give support to a research group of the School of Medicine of the University of Sao Paulo that has been studying asthma using a multidisciplinary approach, with experimental and clinical studies. The central focus of our project is the pulmonary inflammation in asthma and we will perform studies with animal models of pulmonary allergic inflammation, studies with lungs and cell cultures from the lungs of people that died from asthma and also clinical studies with children and adults with asthma. During the planned three years of these studies, we will develop the following protocols: 1. Effects of nitric oxide and capsaicin-sensitive nerve fibers in the modulation of pulmonary inflammation in a guinea pig model of chronic airway inflammation. 2. Effect of capsaicin-sensitive nerve fibers on the airway responsiveness in chronic airway inflammation in different strains of mice with different pulmonary responses to ovalbumin-induced airway inflammation. 3. Effects of BCG on the immune response to ovalbumin in genetically select mice (high and low inflammatory response -AIRmax and AIRmin). 4. Immunomodulation due to short and long-acting beta 2 agonists in a model of chronic airway inflammation in mice. 5. Effects of bronchodilators and inflammatory mediators on airway epithelial ciliary beating frequency and mucociliary transport in mice with pulmonary allergic inflammation. 6. Modulation of chronic airway inflammation by corticosteroids and leukotrienes, including apoptosis of Iymphocytes and eosinophils, using a guinea pig model of chronic airway inflammation. 7. Effects of inflammatory mediators on hyperpnea-induced bronchoconstriction in guinea pigs. 8. Pulmonary nitric oxide synthase expression and activity in experimental models of asthma and chronic obstructive pulmonary disease (COPO) and in people with asthma and COPO. 9. Characteristics of airway inflammation (including upper airways) in people who died from asthma and correlation with clinical data. 10. Apoptosis in culture of smooth muscle cells from airways of people who died from asthma or chronic obstructive pulmonary disease. 11. Role of cytology of nasal aspirate in the evaluation of airway inflammation in adults with asthma. 12. Evaluation of exhaled nitric oxide levels in people without an antecedent of asthma that presented bronchospasm during general anesthesia. 13. Evaluation of airway inflammation during the decreasing in inhaled steroid dosage in children with asthma. 14. Effects of physical training on airway inflammation, functional status and quality of life in children and adults with moderate and severe persistent asthma. (AU)