Structural aspects of airway remodeling in asthma.

Airway remodeling in asthma is a complex process that involves structural changes in virtually all tissues of the airway wall. The histologic changes to the airways consist of epithelial proliferation and goblet cell differentiation, subepithelial fibrosis, airway smooth muscle (ASM) growth, angiogenesis, matrix protein deposition, gland hyperplasia and hypertrophy, and nerve proliferation. Cytokines, chemokines, and growth factors from inflammatory cells and structural cells contribute to remodeling. There are complex interactions among the various signaling pathways involving matrix metalloproteinases that are required for growth factor release. The physiologic consequences of remodeling are airway hyperresponsiveness from ASM growth and mucus hypersecretion from gland and goblet cell hyperplasia. Airway stiffening is a probable contributor to airway hyperresponsiveness through attenuation of the transmission of potently bronchodilating cyclical stress to the ASM during breathing. The epidermal growth factor receptor's role in remodeling and its interaction with other potential causes of remodeling are discussed.