Fibrosis and airway remodelling

The term 'airway remodelling' is now widely used to refer to the developmen t of specific structural changes in the airway wall in asthma. Particular i nterest has focused on subepithelial fibrosis, myofibroblast accumulation, airway smooth muscle hyperplasia and hypertrophy, mucous gland and goblet c ell 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 l evels. Attention also needs to be directed towards the existence of such ch anges in small airways. The natural history of the response has not been we ll described: remodelling is present in the airways of asthmatic children a nd of adults with newly diagnosed asthma, and studies that have attempted t o relate the extent of remodelling to disease severity have produced confli cting 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 frequent ly assumed to be a consequence of chronic inflammation, but the precise rel ation between the remodelling and inflammatory components in asthma is uncl ear. The cellular and molecular events underlying the remodelling process a re also poorly understood. There is therefore a need for the development an d characterization of animal models that will allow these issues to be expl ored. 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 outc ome in asthma but this needs confirmation. Studies addressing the ability o f corticosteroid treatment to reverse established structural changes have n ot produced consistent findings, and there is little information with regar d to other therapies such as theophylline and antileukotriene agents. Effec tive treatment of airway remodelling may require the development of novel t herapies directed against appropriate targets.