Structural changes in the airways in asthma: observations and consequences.
Structural changes reported in the airways of asthmatics include epithelial fragility, goblet cell hyperplasia, enlarged submucosal mucus glands, angiogenesis, increased matrix deposition in the airway wall, increased airway smooth muscle mass, wall thickening and abnormalities in elastin. Genetic influences, as well as fetal and early life exposures, may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of disease and/or long-term uncontrolled inflammation. The increase in smooth muscle mass in both large and small airways probably occurs via multiple mechanisms, and there are probably changes in the phenotype of smooth muscle cells, some showing enhanced synthetic capacity, others enhanced proliferation or contractility. Fixed airflow limitation is probably due to remodelling, whereas the importance of structural changes to the phenomenon of airways hyperresponsiveness may be dependent on the specific clinical phenotype of asthma evaluated. Reduced compliance of the airway wall secondary to enhanced matrix deposition may protect against airway narrowing. Conversely, in severe asthma, disruption of alveolar attachments and adventitial thickening may augment airway narrowing. The encroachment upon luminal area by submucosal thickening may be disadvantageous by increasing the risk of airway closure in the presence of the intraluminal cellular and mucus exudate associated with asthma exacerbations. Structural changes may increase airway narrowing by alteration of smooth muscle dynamics through limitation of the ability of the smooth muscle to periodically lengthen.
Bai
Tony R
TR
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. tbai@mrl.ubc.ca
Knight
Darryl A
DA
D000328:Adult; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D016084:Bronchoconstriction; D002648:Child; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D009093:Mucus / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000502:physiology; D012137:Respiratory System / Q000473:pathology* / Q000503:physiopathology; D013183:Sputum / Q000502:physiology