Effect of bronchoconstriction on airway remodeling in XXXX .

@entity1 @entity32 @entity3045 @entity565 @entity2710
BACKGROUND: Asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to @entity32 . In vitro studies indicate, however, that the compressive mechanical forces that arise during bronchoconstriction may induce remodeling independently of @entity32 . We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in @entity1 with @entity565 . METHODS: We randomly assigned 48 subjects with @entity565 to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and @entity32 ) or @entity2710 (which causes bronchoconstriction without @entity32 ); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or @entity3045 followed by @entity2710 (to control for nonbronchoconstrictor effects of @entity2710 ). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges. RESULTS: Allergen and @entity2710 immediately induced similar levels of bronchoconstriction. Eosinophilic @entity32 of the airways increased only in the allergen group, whereas both the allergen and the @entity2710 groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17  m in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94  m in the @entity2710 group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid-Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the @entity2710 group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and @entity2710 groups. CONCLUSIONS: Bronchoconstriction without additional @entity32 induces airway remodeling in @entity1 with @entity565 . These findings have potential implications for management.
