Fibrosis and airway remodelling.

Abstract

The term 'airway remodelling' is now widely used to refer to the development of specific structural changes in the airway wall in asthma. Particular interest has focused on subepithelial fibrosis, myofibroblast accumulation, airway smooth muscle hyperplasia and hypertrophy, mucous gland and goblet cell hyperplasia, and epithelial disruption. The presence of these features is generally accepted, but further studies are still required to define the changes occurring more precisely at the pathological and ultrastructural levels. Attention also needs to be directed towards the existence of such changes in small airways. The natural history of the response has not been well described: remodelling is present in the airways of asthmatic children and of adults with newly diagnosed asthma, and studies that have attempted to relate the extent of remodelling to disease severity have produced conflicting findings. The role of remodelling in the progressive decline in lung function leading to fixed airflow obstruction seen in some patients is also unclear. Epidemiological studies are currently hindered by the absence of a useful non-invasive marker of remodelling. Airway remodelling is frequently assumed to be a consequence of chronic inflammation, but the precise relation between the remodelling and inflammatory components in asthma is unclear. The cellular and molecular events underlying the remodelling process are also poorly understood. There is therefore a need for the development and characterization of animal models that will allow these issues to be explored. Finally, the ability of currently available anti-asthma therapies to prevent or reverse airway remodelling is uncertain. There is some evidence that early treatment with inhaled corticosteroids can lead to improved outcome in asthma but this needs confirmation. Studies addressing the ability of corticosteroid treatment to reverse established structural changes have not produced consistent findings, and there is little information with regard to other therapies such as theophylline and antileukotriene agents. Effective treatment of airway remodelling may require the development of novel therapies directed against appropriate targets.