Mechanical stimuli to airway remodeling.

The airway is exposed to a variety of mechanical stimuli, the most prominent of which is the acute compressive stress caused by bronchoconstriction. The folding of the airway wall into a rosette pattern during bronchoconstriction creates a complex stress field, with the highest stresses compressing the epithelial layer at the inner surface of the airway wall. The epithelial cells lining the airway possess the capacity to modulate the inflammatory environment of the airway wall, and produce factors that influence the recruitment, proliferation, and activity of fibroblasts and smooth muscle cells. A variety of in vitro studies have demonstrated that airway epithelial cells, along with lung fibroblasts and smooth muscle cells, are responsive to mechanical stimuli. Airway epithelial cells exposed to compressive stresses matched to those occurring in the constricted airway increase expression of genes relevant to airway remodeling, and increase the collagen synthesis of cocultured fibroblasts. These findings demonstrate that mechanical stress may contribute to the remodeling of the asthmatic airway.