Asthma therapy and airway remodeling.
Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways. The most prominent abnormalities include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. In the absence of definite evidence on how different remodeling features affect lung function in asthma, the working hypothesis should be that structural alterations can lead to the development of persistent airway hyperresponsiveness and fixed airway obstruction. It is still unanswered whether and when to begin treating patients with asthma to prevent or reverse deleterious remodeling, which components of remodeling to target, and how to monitor remodeling. Consequently, efforts are being made to understand better the effects of conventional anti-inflammatory therapies, such as glucocorticosteroids, on airway structural changes. Animal models, in vitro studies, and some clinical studies have advanced present knowledge on the cellular and molecular pathways involved in airway remodeling. This has encouraged the development of biologicals aimed to target various components of airway remodeling. Progress in this area requires the explicit linking of modern structure-function analysis with innovative biopharmaceutical approaches.
Mauad
Thais
T
Department of Pathology, São Paulo University Medical School, São Paulo, Brazil.
Bel
Elisabeth H
EH
Sterk
Peter J
PJ
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology*; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology*; D015195:Drug Design; D006801:Humans; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship
D018927:Anti-Asthmatic Agents