[en] Since the 1960s, the prevalence of asthma has increased by 50% per decade worldwide, along with its morbidity, mortality and economic burden. Only in the European Union, the prevalence of asthma doubled during the 1990s, to reach up to 30 million asthmatics by the year 2000, with an annual cost of €17.7 billion for the health systems. Research on asthma pathophysiology and the subsequent therapeutic advances have had a significant impact in the management and control of the disease, yet a portion of approximately 10% of asthmatics still suffer from severe, difficult-to-manage disease, which can be refractory to the maximum available therapy. As a result, asthma has become a research priority for the health systems of the industrialized countries and extensive investigations are being carried out in seek of a better understanding of the disease mechanisms involved, and the development of innovative therapies. From the pathophysiology standpoint, chronic airway inflammation and remodeling underlie the clinical manifestations of asthma. Airway remodeling consists of a series of structural abnormalities that develop in association with chronic inflammation, mostly comprising hyperplasia and hypertrophy of mucus producing cells and glands, subepithelial fibrosis, neovascularization and an increase of airway smooth muscle mass. Data contributed from clinical studies, experimental asthma models and mathematical modeling of airway mechanics have converged into highlighting the increased airway smooth muscle mass as the airway remodeling feature chiefly involved in the mechanism of airway hyperresponsiveness, airflow obstruction and asthma severity. Airway smooth muscle growth in asthma appears to result from a combination of different mechanisms including hyperplasia due to proliferation of resident myocytes, cell hypertrophy, and the recruitment and differentiation of circulating, bone marrow-derived progenitor cells termed fibrocytes. Most of the knowledge on the mechanisms of airway smooth muscle remodeling has been inferred from experimental asthma models and in vitro cell and molecular biology studies, yet such data need translation into the clinical grounds for the advancement of knowledge on the mechanisms of actual human asthma, and for the development of novel treatments. On this front, bronchial biopsy obtained by means of bronchoscopy is the clinical benchmark as a live airway wall sample that allows us to analyze its structure and the immunobiological mechanisms involved in remodeling, at histopathological and ultrastructural level, and by means of in situ cell and molecular biology technologies...

[gl] Dende os anos 60, a prevalencia de asma incrementouse aproximadamente un 50% por década globalmente, xunto coa súa morbilidade, mortalidade e carga económica. Soamente na Unión Europea, a prevalencia de asma dobrouse durante os anos 90, alcanzándose 30 millóns de asmáticos no ano 2000, cun custo anual de 17,7 billóns de euros para os sistemas de saúde. A investigación na fisiopatoloxía da asma e os subseguintes avances terapéuticos tiveron un significativo impacto no manexo e control da enfermidade, aínda que unha proporción de aproximadamente o 10% dos asmáticos aínda padece enfermidade grave de difícil manexo, refractaria á terapia máxima dispoñible. Como resultado, a asma converteuse nunha prioridade de investigación para os sistemas de saúde dos países industrializados e lévanse a cabo extensos traballos en busca dun mellor entendemento dos mecanismos implicados na enfermidade, e do desenvolvemento de terapias innovadoras. Dende o punto de vista fisiopatolóxico, a inflamación crónica e a remodelación das vías respiratorias están baixo as manifestacións clínicas da asma. A remodelación de vías respiratorias consiste nunha serie de anormalidades estruturais que se desenvolven en asociación á inflamación crónica, as cales principalmente inclúen hiperplasia e hipertrofia de células produtoras de moco e glándulas mucosas, fibrose subepitelial, neovascularización e un incremento da masa de músculo liso. Os datos contribuídos por estudos clínicos, modelos de asma experimental e modelado matemático da mecánica de vías respiratorias converxeron en sinalar o crecemento da masa de músculo liso como o compoñente da remodelación de vías respiratorias principalmente implicado no mecanismo da hiperreactividad bronquial, a obstrución ao fluxo aéreo e a gravidade da asma...